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The emerging role of quantitative CT scans in ILD terms
The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?
Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.
The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.
IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).
Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.
Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.
The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?
Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.
The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.
IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).
Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.
Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.
The role of imaging for interstitial lung disease (ILD) is of paramount importance. With the growth of high resolution chest computed tomography (HRCT) imaging techniques, we are able to visualize nuances between individual ILDs more critically. HRCT is an essential component of an initial ILD evaluation and also has become part of the armamentarium of tools used for routine management of these patients. The technology of HRCT scans has evolved over the years, most recently with the advent of quantitative HRCT (qCT). The technology employs texture-based classification, which identifies and quantifies different radiographic findings. The arrival of qCT scanning has been slowly emerging as a new player in the ILD world. What exactly is qCT, and what role can, and will it serve for our ILD patients?
Quantitative CT scanning has been introduced since the 1980s, but only within the last 15 years has its use for ILD taken form. Human interpretation of CTs is fraught with subjectivity, based on the interpreting radiologist’s training, experience, and individual visual perception of images. This can result in significant variability in radiographic interpretations and, ultimately, affects a patient’s diagnosis, disease monitoring, treatment, and prognosis. Semiquantitative visual scoring by radiologists is highly variable, especially in areas with limited availability of chest radiologists. qCT employs an automated histogram signature technique that utilizes density and texture-based analysis of the lung parenchyma. Utilizing machine learning from pathologically confirmed datasets, computer programs were trained with specialized thoracic radiologists to distinguish some commonly found radiographic abnormalities into four major groups: ground glass, reticular, honeycombing, and emphysema. In addition, these categories are quantified and spatially depicted on an analysis (Bartholmai, et al. J Thorac Imaging. 2013;28[5]:298). Various computer programs have been built to streamline the process and expedite the interpretation of an individual’s HRCT scan. The more commonly familiar program, CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Ratings), has been used in multiple research studies of qCT in ILD and IPF. Each patient’s CT scan is uploaded to the program, and a breakdown of the patient’s lungs into each category is presented. Not only is each abnormality quantified and precisely defined, it is also color-coded by segments to help with visual interpretation by the physician.
The benefit of qCT lies not only in the automated, objective evaluation of interstitial lung disease, but also in its possible use in prognostication and mortality prediction. Neither use has been fully validated as of yet. However, growing evidence shows a promising role in both realms. Thus far, there have been some studies correlating PFT data with qCT findings. A follow-up study of the Scleroderma Lung Study II examined qCT changes over 24 months and correlated those findings with PFTs and patient-reported outcomes. Patients in this study were either treated with cyclophosphamide (CYC) for 1 year/placebo 1 year vs mycophenolate mofetil (MMF) for 2 years. A large portion of patients receiving CYC or MMF had a significant correlation between improved or stable qCT scores and their FVC and TLC. Neither CYC nor MMF was superior in qCT scores, aligning with the findings of the study, which showed noninferiority of MMF compared with CYC (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). Interestingly, the improvement of ground glass is often viewed by physicians as positive, since this finding is typically thought of as active inflammation. However, if qCT determines that the fibrosis score actually increases over time, despite an improvement in ground glass, this may more accurately reflect the development of subtle fibrosis that is not easily appreciated by the human eye (Goldin, et al. Ann Am Thorac Soc. 2018 Nov;15[11]:1286). In this context, it is feasible that parenchymal changes occur prior to deterioration on PFTs. Diffusing capacity for carbon monoxide (DLCO) correlates largely with the extent of lung involvement on qCT, but DLCO is not a specific biomarker in predicting severity of ILD (ie, because pHTN or anemia can confound DLCO). Forced vital capacity (FVC) in certain diseases may also confound CT correlation (ie, muscle weakness or extrathoracic restriction from skin disease in systemic sclerosis). The usefulness of PFT data as a clinical endpoint in research studies may be replaced by qCTs more consistent and precise detection of disease modification.
IPF has been an interesting area of exploration for the role of qCT in disease monitoring and possible prognostication. It is known that the presence of honeycombing on HRCT is associated with increased mortality. Patients with a progressive fibrotic ILD have similar mortality rates to those with IPF (Adegunsoye, et al. Ann Am Thorac Soc. 2019 May;16[5]:580). The ability to correlate radiographic findings with mortality could potentially become an important marker of clinical deterioration, especially in those patients who are unable to perform PFTs. In addition, it can also be beneficial in those with co-existent emphysema, since PFTs may be confounded by this overlap. Nakagawa and colleagues proposed a computer-aided method for qCT analysis of honeycombing in patients with IPF. The algorithm for the qCT analysis also has specific parameters to exclude emphysematous lesions on imaging. The %honeycomb area (HA) was correlated with a composite physiologic index derived from PFTs (calculated from FEV1, FVC and DLCO). This tool can accurately quantify the percentage of honeycombing and aid in monitoring IPF. Using this protocol, Nakagawa was able to demonstrate a significant correlation with 3-year mortality, with a marked difference found when using a cutoff value of 4.8% (Nakagawa, et al. Plos One. 2019 Mar; 14[3]:e0214278). Furthermore, patient survival in IPF has been compared against the CALIPER program and PFTs. Mortality for patients was significantly associated with pulmonary vessel volume (PVV), an innovative tool that quantified the volume of the pulmonary artery and veins, which may become a new parameter used for disease monitoring. Using qCT in addition to PFTs provides more tangible evidence to help monitor patients with IPF, guide treatment decisions, and plan for transplant or palliative care. The growing use of PVV in qCT has yet to be fully elucidated, but it does have a promising role (Jacob, et al. Eur Respir J. 2017;49[1]. doi: 10.1183/13993003.01011-2016).
Despite the positive outlook for qCT, there are major issues that limit its widespread use. During the image acquisition process, there is a lack of consistency and quality control, stemming from multiple different manufacturers of CT scan machines, reconstitution methods, radiation doses, and noise or inspiratory efforts of patients. The Radiologic Society of North America (RSNA) is attempting to fix this issue by creating a standardized protocol for collecting images used for qCT (Castillo-Saldana, et al. J Thorac Imaging. 2019 Aug 7. doi: 10.1097/RTI.0000000000000440). In order to move forward with adaptation of qCT, a standardized approach and handling of images needs to be created.
Quantitative CT is an exciting new prospect for the care of patients with ILD. As these patients, and their management, becomes more complex, expanding the toolbox for physicians is much needed. It will be fascinating to see how the role of qCT takes shape over the coming years.
Dr. D’Annunzio is with Westmed Medical Group, Rye, N.Y.; Dr. Nayar is a Pulmonary/Critical Care Fellow at NYU School of Medicine; and Dr. Patel is with Columbia University Medical Center.
Dysregulated sleep is common in children with eosinophilic esophagitis
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
, Rasintra Siriwat, MD, and colleagues have ascertained.
Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.
The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m2. A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.
Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.
Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).
All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.
“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.
The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).
Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.
“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”
Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.
SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.
FROM SLEEP MEDICINE
FDA approves benralizumab autoinjector for eosinophilic asthma
according to a press release from AstraZeneca. Benralizumab is already approved as add-on maintenance for this form of asthma, but not for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.
The autoinjector “pen” was tested for usability and pharmacokinetic exposure in two studies, the phase 3 GRECO trial and the phase 1 AMES trial, respectively. The multicenter, open-label GRECO trial was designed to assess patient- or caregiver-reported functionality, and it found that 97% of at-home administrations were successful at week 12 and week 16. The multicenter, randomized, open-label, parallel-group AMES trial compared pharmacokinetic exposure with the subcutaneous administration using either prefilled syringe or prefilled autoinjector; it found that the eosinophils were rapidly depleted in patients with use of either device.
The safety profiles in both trials were comparable to those seen in previous trials. Hypersensitivity reactions have been sometimes observed in the hours following administration of benralizumab; discontinuation is advised in case of any hypersensitivity reaction. The therapy should not be used to treat acute asthma symptoms, such as exacerbations, or bronchospasm, and any reduction in corticosteroid therapy should be gradual and performed under careful supervision of a health care professional. Although benralizumab’s effects on helminth infections are currently unknown, care should be taken with preexisting or incident infections.
Full prescribing information can be found on the AstraZeneca website.
according to a press release from AstraZeneca. Benralizumab is already approved as add-on maintenance for this form of asthma, but not for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.
The autoinjector “pen” was tested for usability and pharmacokinetic exposure in two studies, the phase 3 GRECO trial and the phase 1 AMES trial, respectively. The multicenter, open-label GRECO trial was designed to assess patient- or caregiver-reported functionality, and it found that 97% of at-home administrations were successful at week 12 and week 16. The multicenter, randomized, open-label, parallel-group AMES trial compared pharmacokinetic exposure with the subcutaneous administration using either prefilled syringe or prefilled autoinjector; it found that the eosinophils were rapidly depleted in patients with use of either device.
The safety profiles in both trials were comparable to those seen in previous trials. Hypersensitivity reactions have been sometimes observed in the hours following administration of benralizumab; discontinuation is advised in case of any hypersensitivity reaction. The therapy should not be used to treat acute asthma symptoms, such as exacerbations, or bronchospasm, and any reduction in corticosteroid therapy should be gradual and performed under careful supervision of a health care professional. Although benralizumab’s effects on helminth infections are currently unknown, care should be taken with preexisting or incident infections.
Full prescribing information can be found on the AstraZeneca website.
according to a press release from AstraZeneca. Benralizumab is already approved as add-on maintenance for this form of asthma, but not for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.
The autoinjector “pen” was tested for usability and pharmacokinetic exposure in two studies, the phase 3 GRECO trial and the phase 1 AMES trial, respectively. The multicenter, open-label GRECO trial was designed to assess patient- or caregiver-reported functionality, and it found that 97% of at-home administrations were successful at week 12 and week 16. The multicenter, randomized, open-label, parallel-group AMES trial compared pharmacokinetic exposure with the subcutaneous administration using either prefilled syringe or prefilled autoinjector; it found that the eosinophils were rapidly depleted in patients with use of either device.
The safety profiles in both trials were comparable to those seen in previous trials. Hypersensitivity reactions have been sometimes observed in the hours following administration of benralizumab; discontinuation is advised in case of any hypersensitivity reaction. The therapy should not be used to treat acute asthma symptoms, such as exacerbations, or bronchospasm, and any reduction in corticosteroid therapy should be gradual and performed under careful supervision of a health care professional. Although benralizumab’s effects on helminth infections are currently unknown, care should be taken with preexisting or incident infections.
Full prescribing information can be found on the AstraZeneca website.
Histologic analysis of vaping-associated lung injury suggests chemical pneumonitis
Vaping-associated lung injury is likely a form of airway-centered chemical pneumonitis, not exogenous lipoid pneumonia, according to Yasmeen M. Butt, MD, of the University of Texas Southwestern Medical Center, Dallas, and associates.
Dr. Butt and associates performed a review of lung biopsies from 17 patients (13 men; median age, 35 years) with a history of vaping and either suspected or confirmed vaping-associated lung injury. All cases showed patterns of acute lung injury, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, the authors noted in a letter to the editor published in the New England Journal of Medicine.
While no histologic findings were specific, foamy macrophages and pneumocyte vacuolization were seen in all cases, the authors added. Pigmented macrophages were occasionally present but not dominant, neutrophils were often prominent, eosinophils were rare, and granulomas were not seen. Two patients eventually died, despite treatment with glucocorticoids and maximum supportive care.
“None of our cases showed histologic evidence of exogenous lipoid pneumonia and no radiologic evidence thereof has been found; this calls into question the diagnostic utility of identifying lipid-laden macrophages or performing oil red O staining on bronchioloalveolar lavage fluid as a marker of vaping-associated lung injury, as has been proposed,” Dr. Butt and associates wrote.
No conflicts of interest were reported.
SOURCE: Butt YM et al. N Engl J Med. 2019 Oct 2. doi: 10.1056/NEJMc1913069.
Vaping-associated lung injury is likely a form of airway-centered chemical pneumonitis, not exogenous lipoid pneumonia, according to Yasmeen M. Butt, MD, of the University of Texas Southwestern Medical Center, Dallas, and associates.
Dr. Butt and associates performed a review of lung biopsies from 17 patients (13 men; median age, 35 years) with a history of vaping and either suspected or confirmed vaping-associated lung injury. All cases showed patterns of acute lung injury, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, the authors noted in a letter to the editor published in the New England Journal of Medicine.
While no histologic findings were specific, foamy macrophages and pneumocyte vacuolization were seen in all cases, the authors added. Pigmented macrophages were occasionally present but not dominant, neutrophils were often prominent, eosinophils were rare, and granulomas were not seen. Two patients eventually died, despite treatment with glucocorticoids and maximum supportive care.
“None of our cases showed histologic evidence of exogenous lipoid pneumonia and no radiologic evidence thereof has been found; this calls into question the diagnostic utility of identifying lipid-laden macrophages or performing oil red O staining on bronchioloalveolar lavage fluid as a marker of vaping-associated lung injury, as has been proposed,” Dr. Butt and associates wrote.
No conflicts of interest were reported.
SOURCE: Butt YM et al. N Engl J Med. 2019 Oct 2. doi: 10.1056/NEJMc1913069.
Vaping-associated lung injury is likely a form of airway-centered chemical pneumonitis, not exogenous lipoid pneumonia, according to Yasmeen M. Butt, MD, of the University of Texas Southwestern Medical Center, Dallas, and associates.
Dr. Butt and associates performed a review of lung biopsies from 17 patients (13 men; median age, 35 years) with a history of vaping and either suspected or confirmed vaping-associated lung injury. All cases showed patterns of acute lung injury, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, the authors noted in a letter to the editor published in the New England Journal of Medicine.
While no histologic findings were specific, foamy macrophages and pneumocyte vacuolization were seen in all cases, the authors added. Pigmented macrophages were occasionally present but not dominant, neutrophils were often prominent, eosinophils were rare, and granulomas were not seen. Two patients eventually died, despite treatment with glucocorticoids and maximum supportive care.
“None of our cases showed histologic evidence of exogenous lipoid pneumonia and no radiologic evidence thereof has been found; this calls into question the diagnostic utility of identifying lipid-laden macrophages or performing oil red O staining on bronchioloalveolar lavage fluid as a marker of vaping-associated lung injury, as has been proposed,” Dr. Butt and associates wrote.
No conflicts of interest were reported.
SOURCE: Butt YM et al. N Engl J Med. 2019 Oct 2. doi: 10.1056/NEJMc1913069.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Oral drug cut viral respiratory tract infections in elderly
WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.
At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.
During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.
RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.
The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.
The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.
The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.
The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.
WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.
At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.
During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.
RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.
The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.
The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.
The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.
The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.
WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.
At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.
During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.
RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.
The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.
The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.
The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.
The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.
REPORTING FROM IDWEEK 2019
Massachusetts tops state vaccination rankings
according to a new analysis from personal finance website WalletHub.
The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.
The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.
Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.
“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”
according to a new analysis from personal finance website WalletHub.
The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.
The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.
Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.
“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”
according to a new analysis from personal finance website WalletHub.
The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.
The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.
Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.
“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”
Vaping-associated lung injury cases exceed 1,000
More than 1,000 cases of vaping-associated lung injury have been reported in 48 states and the U.S. Virgin Islands, according to a telebriefing by the Centers for Disease Control and Prevention.
As of Oct. 1, there have been 1,080 confirmed and probable cases of lung injury associated with the use of e-cigarettes, or vaping, said Anne Schuchat, MD, principal deputy director of the CDC. The latest figures were also reported in a statement issued by the CDC.
Dr. Schuchat said 18 related deaths in 15 states have been confirmed, and additional deaths are under investigation.
“As we have continued to get data for additional cases, the trends we reported last week persist,” Dr. Schuchat said (MMWR. 2019 Sep 27;68[39];860-4).
“Most patients reported a history of using THC [tetrahydrocannabinol]-containing products, and most patients are male and young people.” Of the 1,080 cases identified, approximately 70% are male, roughly 80% are younger than 35 years of age, and 37% are under 21 years of age. The patients’ median age is 23 years (range, 13-75 years). Among patients who have died, the median age is 50 years (range, 27-71 years).
The CDC now has information from 578 patients on the substances used in vaping products in the 90 days before symptom onset. About 78% of these patients reported using THC-containing products, and 37% reported exclusive use of THC-containing products. Roughly 58% of patients reported using nicotine-containing products, and 17% reported exclusive use of nicotine-containing products.
“I wish we had more answers regarding the specific harmful products or components that are causing these illnesses,” Dr. Schuchat said. She noted that THC-containing products appear to be the most commonly used, but these products don’t appear to be the only culprit. Additionally, in a report released recently in the New England Journal of Medicine (2019 Sep 9. doi: 10.1056/NEJMoa1911614), THC-containing products bought “off the street” were commonly used by patients with lung injuries. However, the CDC can’t say for certain if it’s safer for consumers to buy THC-containing products from a licensed dispensary.
The CDC has deployed staff to several states to help investigate the lung injuries, reached out to the clinical community to increase awareness of the injuries, and worked with clinicians and medical examiners to review assessments of patients who have developed these injuries, including those who have died. The CDC has also convened clinical professional societies to “help strengthen the detection, reporting, and management of cases,” Dr. Schuchat said.
In addition, the CDC has joined with the Food and Drug Administration and other public health partners to develop a laboratory plan for “continued testing of products, aerosol testing of substances produced by the products, and clinical pathology lung specimens from patients,” Dr. Schuchat said.
The FDA is also working to gather more information about vaping-associated lung injuries. The FDA is trying to obtain “critical details” about the specific products or substances that may be involved, said Judy McMeekin, PharmD, deputy associate commissioner for regulatory affairs at the FDA.
“There does not currently appear to be one product or substance involved in all of the cases,” Dr. McMeekin said. “We are leaving no stone unturned and following all potential leads regarding any particular product, constituent, or compound that may be at issue.”
The FDA has collected more than 440 samples of vaping devices and products from 18 states. The agency is still analyzing these samples, but a preliminary analysis has shown that some products contain THC concentrations ranging from 14% to 76%, and some products contain a combination of THC and vitamin E acetate ranging from 31% to 88%.
For information about the collection of vaping products for possible testing by the FDA, email [email protected]. For information about collection and submission of clinical specimens for possible testing by the CDC, see the Healthcare Provider webpage.
Clinicians and health officials who have questions about this outbreak can email [email protected]. All others with questions about this outbreak can contact CDC-INFO at 800-232-4636 or submit information at the Contact CDC-INFO page.
More than 1,000 cases of vaping-associated lung injury have been reported in 48 states and the U.S. Virgin Islands, according to a telebriefing by the Centers for Disease Control and Prevention.
As of Oct. 1, there have been 1,080 confirmed and probable cases of lung injury associated with the use of e-cigarettes, or vaping, said Anne Schuchat, MD, principal deputy director of the CDC. The latest figures were also reported in a statement issued by the CDC.
Dr. Schuchat said 18 related deaths in 15 states have been confirmed, and additional deaths are under investigation.
“As we have continued to get data for additional cases, the trends we reported last week persist,” Dr. Schuchat said (MMWR. 2019 Sep 27;68[39];860-4).
“Most patients reported a history of using THC [tetrahydrocannabinol]-containing products, and most patients are male and young people.” Of the 1,080 cases identified, approximately 70% are male, roughly 80% are younger than 35 years of age, and 37% are under 21 years of age. The patients’ median age is 23 years (range, 13-75 years). Among patients who have died, the median age is 50 years (range, 27-71 years).
The CDC now has information from 578 patients on the substances used in vaping products in the 90 days before symptom onset. About 78% of these patients reported using THC-containing products, and 37% reported exclusive use of THC-containing products. Roughly 58% of patients reported using nicotine-containing products, and 17% reported exclusive use of nicotine-containing products.
“I wish we had more answers regarding the specific harmful products or components that are causing these illnesses,” Dr. Schuchat said. She noted that THC-containing products appear to be the most commonly used, but these products don’t appear to be the only culprit. Additionally, in a report released recently in the New England Journal of Medicine (2019 Sep 9. doi: 10.1056/NEJMoa1911614), THC-containing products bought “off the street” were commonly used by patients with lung injuries. However, the CDC can’t say for certain if it’s safer for consumers to buy THC-containing products from a licensed dispensary.
The CDC has deployed staff to several states to help investigate the lung injuries, reached out to the clinical community to increase awareness of the injuries, and worked with clinicians and medical examiners to review assessments of patients who have developed these injuries, including those who have died. The CDC has also convened clinical professional societies to “help strengthen the detection, reporting, and management of cases,” Dr. Schuchat said.
In addition, the CDC has joined with the Food and Drug Administration and other public health partners to develop a laboratory plan for “continued testing of products, aerosol testing of substances produced by the products, and clinical pathology lung specimens from patients,” Dr. Schuchat said.
The FDA is also working to gather more information about vaping-associated lung injuries. The FDA is trying to obtain “critical details” about the specific products or substances that may be involved, said Judy McMeekin, PharmD, deputy associate commissioner for regulatory affairs at the FDA.
“There does not currently appear to be one product or substance involved in all of the cases,” Dr. McMeekin said. “We are leaving no stone unturned and following all potential leads regarding any particular product, constituent, or compound that may be at issue.”
The FDA has collected more than 440 samples of vaping devices and products from 18 states. The agency is still analyzing these samples, but a preliminary analysis has shown that some products contain THC concentrations ranging from 14% to 76%, and some products contain a combination of THC and vitamin E acetate ranging from 31% to 88%.
For information about the collection of vaping products for possible testing by the FDA, email [email protected]. For information about collection and submission of clinical specimens for possible testing by the CDC, see the Healthcare Provider webpage.
Clinicians and health officials who have questions about this outbreak can email [email protected]. All others with questions about this outbreak can contact CDC-INFO at 800-232-4636 or submit information at the Contact CDC-INFO page.
More than 1,000 cases of vaping-associated lung injury have been reported in 48 states and the U.S. Virgin Islands, according to a telebriefing by the Centers for Disease Control and Prevention.
As of Oct. 1, there have been 1,080 confirmed and probable cases of lung injury associated with the use of e-cigarettes, or vaping, said Anne Schuchat, MD, principal deputy director of the CDC. The latest figures were also reported in a statement issued by the CDC.
Dr. Schuchat said 18 related deaths in 15 states have been confirmed, and additional deaths are under investigation.
“As we have continued to get data for additional cases, the trends we reported last week persist,” Dr. Schuchat said (MMWR. 2019 Sep 27;68[39];860-4).
“Most patients reported a history of using THC [tetrahydrocannabinol]-containing products, and most patients are male and young people.” Of the 1,080 cases identified, approximately 70% are male, roughly 80% are younger than 35 years of age, and 37% are under 21 years of age. The patients’ median age is 23 years (range, 13-75 years). Among patients who have died, the median age is 50 years (range, 27-71 years).
The CDC now has information from 578 patients on the substances used in vaping products in the 90 days before symptom onset. About 78% of these patients reported using THC-containing products, and 37% reported exclusive use of THC-containing products. Roughly 58% of patients reported using nicotine-containing products, and 17% reported exclusive use of nicotine-containing products.
“I wish we had more answers regarding the specific harmful products or components that are causing these illnesses,” Dr. Schuchat said. She noted that THC-containing products appear to be the most commonly used, but these products don’t appear to be the only culprit. Additionally, in a report released recently in the New England Journal of Medicine (2019 Sep 9. doi: 10.1056/NEJMoa1911614), THC-containing products bought “off the street” were commonly used by patients with lung injuries. However, the CDC can’t say for certain if it’s safer for consumers to buy THC-containing products from a licensed dispensary.
The CDC has deployed staff to several states to help investigate the lung injuries, reached out to the clinical community to increase awareness of the injuries, and worked with clinicians and medical examiners to review assessments of patients who have developed these injuries, including those who have died. The CDC has also convened clinical professional societies to “help strengthen the detection, reporting, and management of cases,” Dr. Schuchat said.
In addition, the CDC has joined with the Food and Drug Administration and other public health partners to develop a laboratory plan for “continued testing of products, aerosol testing of substances produced by the products, and clinical pathology lung specimens from patients,” Dr. Schuchat said.
The FDA is also working to gather more information about vaping-associated lung injuries. The FDA is trying to obtain “critical details” about the specific products or substances that may be involved, said Judy McMeekin, PharmD, deputy associate commissioner for regulatory affairs at the FDA.
“There does not currently appear to be one product or substance involved in all of the cases,” Dr. McMeekin said. “We are leaving no stone unturned and following all potential leads regarding any particular product, constituent, or compound that may be at issue.”
The FDA has collected more than 440 samples of vaping devices and products from 18 states. The agency is still analyzing these samples, but a preliminary analysis has shown that some products contain THC concentrations ranging from 14% to 76%, and some products contain a combination of THC and vitamin E acetate ranging from 31% to 88%.
For information about the collection of vaping products for possible testing by the FDA, email [email protected]. For information about collection and submission of clinical specimens for possible testing by the CDC, see the Healthcare Provider webpage.
Clinicians and health officials who have questions about this outbreak can email [email protected]. All others with questions about this outbreak can contact CDC-INFO at 800-232-4636 or submit information at the Contact CDC-INFO page.
One-third of patients with severe asthma are overusing corticosteroids
MADRID – if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.
“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.
In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.
Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.
In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.
On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,
When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.
Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.
“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.
The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.
“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.
In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.
“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”
Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.
Dr. Eger reports no potential conflicts of interest.
MADRID – if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.
“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.
In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.
Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.
In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.
On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,
When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.
Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.
“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.
The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.
“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.
In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.
“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”
Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.
Dr. Eger reports no potential conflicts of interest.
MADRID – if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.
“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.
In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.
Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.
In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.
On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,
When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.
Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.
“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.
The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.
“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.
In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.
“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”
Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.
Dr. Eger reports no potential conflicts of interest.
REPORTING FROM ERS 2019
IPD in children may be a signal of immunodeficiency
according to a systematic review published in JAMA Pediatrics.
Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.
They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.
Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.
One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).
Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.
The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.
Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.
In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.
Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”
In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.
“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.
No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.
SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.
according to a systematic review published in JAMA Pediatrics.
Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.
They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.
Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.
One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).
Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.
The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.
Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.
In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.
Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”
In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.
“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.
No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.
SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.
according to a systematic review published in JAMA Pediatrics.
Coen Butters, BMed, DCH, of the Royal Children’s Hospital in Melbourne, and coauthors wrote that, even with optimal vaccine coverage, there is still a group of children with increased susceptibility to invasive pneumococcal disease (IPD), and this could be a potential marker of primary immunodeficiency.
They conducted a systematic review of 17 studies of 6,002 children to examine the evidence on the incidence of primary immunodeficiency in children who presented with IPD but without any other risk factors or predisposing conditions.
Overall, the frequency of primary immunodeficiency in children presenting with IPD who did not have any other predisposing condition ranged from 1% to 26%.
One study of 162 children with IPD, which had an overall frequency of primary immunodeficiency of 10%, found that children older than 2 years were significantly more likely to have primary immunodeficiency than those aged under 2 years (26% vs. 3%; P less than .001).
Primary antibody deficiency was the most commonly diagnosed immunodeficiency in these children with IPD, accounting for 71% of cases. These deficiencies presented as hypogammaglobulinemia, specific pneumococcal antibody deficiency, X-linked agammaglobulinemia, and IgG2 deficiency.
The review also included four studies that looked at the frequency of mannose-binding lectin deficiency in 1,493 children with primary IPD. Two of these studies reported a prevalence of mannose-binding lectin deficiency ranging from 31% in children aged younger than 2 years to 41% in children younger than 1 year.
Five studies looked at the rate of primary immunodeficiency in children presenting with recurrent IPD. In addition to other predisposing conditions such as sickle cell disease, cancer, and anatomical breach in the blood-brain barrier, the three studies that screened for primary immunodeficiency found rates ranging from 10% to 67%. The most common conditions were complement deficiency, pneumococcal antibody deficiency, and a single case of TLR-signaling defect.
In a study of 162 children with primary IPD, screening for asplenia identified a single case of congenital asplenia. In another study of 2,498 cases of IPD, 22 patients had asplenia at presentation, half of whom died at presentation.
Dr. Butters and associates concluded that “this review’s findings suggests that existing data support the immune evaluation of children older than 2 years without a known predisposing condition who present with their first episode of Streptococcus pneumoniae meningitis, pneumonia, or recurrent IPD. Immune evaluation should include assessment for immunoglobulin deficiency, pneumococcal antibody deficiency, complement disorders, and asplenia.”
In an accompanying editorial, Stephen I. Pelton, MD, of the Maxwell Finland Laboratory for Infectious Diseases at Boston Medical Center, and coauthors wrote that in children with recurrent episodes of IPD caused by nonvaccine serotypes – particularly those aged over 5 years – evaluation for primary immunodeficiencies could uncover immune defects.
“Once identified, direct and indirect protection, penicillin prophylaxis, or a combination of these offers great potential for disease prevention and reduction of mortality and morbidity in children with [primary immunodeficiency],” they wrote.
No funding or conflicts of interest were declared for the study. Two of the editorialists declared research funding or honoraria from the pharmaceutical sector.
SOURCES: Butters C et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3203; Pelton SI et al. JAMA Pediatr. 2019 Sep 30. doi: 10.1001/jamapediatrics.2019.3185.
FROM JAMA PEDIATRICS