Cystic Fibrosis

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — With the remarkable advances made in therapy over the past decade, many patients with cystic fibrosis (CF) can expect to survive into their 50s and even well beyond. But as patients with CF live longer, they are increasingly likely to develop complications such as cardiovascular diseases (CVDs) that beset many older adults. And as evidence from a new study suggests, there is an increasing need for cardiovascular screening and specialized cardiac care for these patients.

Among more than 83,000 patients with CF hospitalized for any reason from 2016 through 2021, less than 1% of patients had a cardiac cause listed, but in unadjusted analyses, these patients had a more than twofold risk for in-hospital death than those with CF hospitalized for other causes, reported Adnan Bhat, MD, assistant professor of hospital medicine at the University of Florida, Gainesville.

Although the excess mortality was no longer statistically significant in analyses adjusted for potential confounding factors, the data highlight a trend that requires further exploration, he said during an oral abstract session at the annual meeting of the American College of Chest Physicians (CHEST).

“There’s a trend for people with cystic fibrosis admitted for cardiac causes to have a higher in-hospital mortality and increased rate of discharge to nursing facilities, especially for patients admitted for heart failure. The clinical implication is that there is an increased need to start screening for cardiovascular risk factors,” he said.
 

National Database Sample

Bhat and colleagues conducted a retrospective study using the National Inpatient Sample database to identify all hospitalizations among patients with CF in the United States from 2016 through 2021.

They included all hospitalizations with a principal diagnosis code for atrial fibrillation, heart failure, or myocardial infarction.

Of 83,250 total hospitalizations during the study period, 415 (0.5%) were for primary cardiac causes. These included 170 hospitalizations for atrial fibrillation, 95 for heart failure, and 150 for myocardial infarction.

Patients hospitalized for cardiac causes had a higher mean age (59.5 vs 34.5 years) and more comorbidities than patients hospitalized for other causes. These comorbidities included hyperlipidemia, chronic kidney disease, obesity, and a family history of coronary artery disease.

In all, 5% of patients hospitalized for cardiac cause died in hospital, compared with 2% of patients hospitalized for other reasons (P = .044).

However, in logistic regression analyses adjusting for age, sex, and race, this difference was no longer significant.

Similarly, an unadjusted analysis showed that patients with cardiac disease were twice as likely to be discharged to a nursing facility (8% vs 4%, respectively), but this difference too disappeared in adjusted analyses.

The risk for in-hospital mortality appeared to be highest among those patients with a primary diagnosis of heart failure, who had an 11% rate of in-hospital death, compared with 2% among patients with CF hospitalized for other causes.

The total number of deaths was too small, however, to allow for regression analysis, Bhat said.

Nonetheless, taken together, the data indicate a trend toward increased mortality from cardiovascular causes among older patients with CF, as well as the need for further research into the cardiovascular health of these patients, Bhat concluded.
 

Better Nutrition, Higher Risk

In an interview, Yuqing A. Gao, MD, from the Santa Monica Pulmonary Sleep Clinic in California, who was not involved in the study, commented that with the advent of elexacaftor/tezacaftor/ivacaftor modulator therapy, patients with CF tend to have increases in body mass index and improved nutritional intake and absorption, which in turn could increase hyperlipidemia and other factors that might in turn contribute to increased CVD risk.

“It’s really an interesting area of research, and there’s hope that this will bring more focus on how to better screen [for CVD risk] because that’s something that’s very much not known at this time,” she said.

Gao was co-moderator for the session where Bhat presented the data. Bhat did not report a study funding source. Bhat and Gao reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
 

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
 

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
• In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
 

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
 

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
• In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
 

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
 

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
• In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

After Rena Barrow-Wells, an African American mother, fought mightily to prevent a repeat of her experience of two decades earlier when her first child’s cystic fibrosis (CF) took 4 years to diagnose, her story became the subject of a New York Times feature covering disparities in diagnostic CF screening. The article highlighted not only her struggles, but also the utter transformation of the CF landscape since the introduction of small molecule mutation-specific drugs. These drugs restore function to defective CF transmembrane conductance regulator (CFTR) proteins. By the time Ms. Barrow-Wells’ young son was treated, lung and pancreatic scarring were already significant. So when the 39-mutation variant screening test available in Ms. Barrow-Wells’ Lawrenceville, Georgia, clinic turned out negative for CF, her pediatrician told her to stop worrying despite her new son’s inherent genetic risk, telltale salty skin, foul-smelling diapers, and her pleas to test for sweat chloride. It still took 3 months for a confirmed diagnosis and the initiation of treatment.

Current genetic tests, based largely on older clinical trials that enrolled mostly white children, are highly accurate for identifying CF in white babies (95%), but often fail to identify substantial percentages of mutations originating in Africa, Asia, and Latin America. They miss CF in Asian (44%), Black (22%), and Hispanic, Native American and Alaskan Native babies (14%), the Times article stated. In the United States, the number of CF variants tested for falls into a wide range: from the one variant found mostly in White populations in Mississippi (with a 38% Black populace) to 689 variants in Wisconsin.

Callista Images/Image Source/Getty Images

Today’s CF challenges

Beyond refinements in screening instruments and policies that broaden access leading to the earliest possible diagnoses, ongoing research needs include finding treatments for other variants, and caring for adult populations living with treated CF and the disease’s multisystem manifestations. “As people with CF live longer, we need to be very focused on optimized adult medical care for this population,” Marc A. Sala, MD, assistant professor of medicine, Adult CF Program, Northwestern University Feinberg School of Medicine, Chicago, said in an interview. “For example, we need higher vigilance for liver, microvascular, coronary artery disease, and various cancer screenings. We do not know exactly how these will manifest differently from the way they do in non-CF populations, so this is where more work needs to be done.”

Northwestern University Feinberg School of Medicine

Emphasis on monitoring

The authors of “Future therapies for cystic fibrosis” (Allen et al. Nature Communications, 2023 Feb 8), after citing the ongoing transformative change for people with CF since the introduction of CFTR drugs, gave voice to important cautions. “Disease will progress, albeit more slowly, and will be more challenging to monitor. Effective CFTR modulators will likely slow or, at best, halt disease progression, but will not reverse a disease that has already become fixed.” They cited pancreatic destruction in the majority, bronchiectasis, and absence of the vas deferens, with still recurring (although less frequently) pulmonary exacerbations along with chronic infections and persistent airway inflammation. “It is essential that we do not become complacent about disease progression in this population,” the researchers stated. They cautioned also that effective surveillance for infection is critical in asymptomatic patients, emphasizing that it underpins the management of young healthy children with CF who demonstrate disease progression despite a lack of symptoms.

Among the ~90% for whom Trikafta is suitable and approved (those with least one copy of F508del or specific other responsive mutations), improvements include increased percent predicted FEV₁ by 10%-15% or more, decreased exacerbations, and improved quality of life,” Dr. Sala said. “Subsequent ‘real world’ experience shows dramatic reductions in sputum production and decreased frequency of lung transplant.”
 

Mutation agnostic therapy

Unfortunately, CF mutants, outside the population eligible for Trikafta, are prodigious in number and do not fall into just a few major groups. “Furthermore, although CF is a monogenic disease, it has variable phenotypes even for two individuals with the same mutations,” Dr. Sala said. “Current CFTR modulators act on the dysfunctional CFTR protein (either as channel gating potentiators or molecular chaperones to improve misfolding). That leaves about 10% of the CF population, those with little to no protein production (such as in nonsense mutations) ineligible for treatment with CFTR modulators. “The ideal for efficacy and equity, given that some CFTR mutations only exist in a handful of people, would be to develop a ‘mutation agnostic’ strategy — such as with mRNA or gene delivery. Here you could imagine that regardless of the type of mutation, a patient would then be able to receive the technology to increase CFTR channel function,” Dr. Sala said. Many modifiable factors, including host immunity and non-CFTR genes that impact CFTR indirectly, may underlie the fact that one person has a worse trajectory than another. “New therapies may also be found in this area of research,” Dr. Sala said.

Strategies in testing phases

“For patients with class I (nonsense) mutations there is hope that small molecules will be identified that can facilitate premature truncation codon (PTC) read-through and/or impede mRNA decay allowing for clinically relevant levels of functional CFTR,” the researchers noted. While the most extensively developed, ataluren, an oxadiazole, failed in phase 3 trials after initial promise, other ribosomal read-through drugs are in preclinical and early phase clinical trials. Also, early encouraging results support an alternative strategy, engineered transfer RNAs (tRNAs) that introduce an amino acid to an elongating peptide in place of the termination codon.

While these will address specific mutations, DNA or mRNA replacement strategies would be “mutation agnostic,” the researchers stated. The major challenge: delivery to the respiratory epithelium. Approaches currently in early testing include an inhaled aerosolized, lipid-based nanoparticle carrier for mRNA delivery, viral and non-viral DNA transfer, lipid-mediated CFTR gene transfer, pseudotyped lentiviral vector and adeno-associated vector transfer of CFTR DNA.
 

Adult CF care

“Adult CF care in general is a completely new frontier,” Meilinh Thi, DO, director of the adult cystic fibrosis program and assistant professor at University of Texas Health at San Antonio, said in an interview. “It’s fairly new to have separate pediatric and adult CF centers. There’s been a shift,” she said. “We’re encountering diseases in CF that we have not in the past had to deal with: diabetes that has features of both type 1 and type 2, increased colon cancer risk, bone disease, and mental health issues. Also, while pregnancy was previously discouraged for women with CF because of lung disease, now many are giving birth without complications and living normal lives,” Dr. Thi said.

University of Texas Health at San Antonio

“We do encourage our patients to talk to us before becoming pregnant so we can discuss the risk of passing on the gene. And, we do encourage their significant others to get testing. Some patients and their others, however, do decline to get tested,” she added.

The lifetime health issues conferred by CF, Dr. Thi noted, include lung disease with chronic inflammation, infection, respiratory failure (still the most common cause of death), gastrointestinal disorders (including of the pancreas) , colon obstruction and colon cancer, sinus disease, and reproductive system effects. Their permanence, she said, depends on how far their disease has progressed. “So the earlier you can provide these newer therapies — the modulators, for example, or the gene therapy whenever that comes out, then the less damage these organ systems will have, and the patients, we hope, will then do better.”

After Rena Barrow-Wells, an African American mother, fought mightily to prevent a repeat of her experience of two decades earlier when her first child’s cystic fibrosis (CF) took 4 years to diagnose, her story became the subject of a New York Times feature covering disparities in diagnostic CF screening. The article highlighted not only her struggles, but also the utter transformation of the CF landscape since the introduction of small molecule mutation-specific drugs. These drugs restore function to defective CF transmembrane conductance regulator (CFTR) proteins. By the time Ms. Barrow-Wells’ young son was treated, lung and pancreatic scarring were already significant. So when the 39-mutation variant screening test available in Ms. Barrow-Wells’ Lawrenceville, Georgia, clinic turned out negative for CF, her pediatrician told her to stop worrying despite her new son’s inherent genetic risk, telltale salty skin, foul-smelling diapers, and her pleas to test for sweat chloride. It still took 3 months for a confirmed diagnosis and the initiation of treatment.

Current genetic tests, based largely on older clinical trials that enrolled mostly white children, are highly accurate for identifying CF in white babies (95%), but often fail to identify substantial percentages of mutations originating in Africa, Asia, and Latin America. They miss CF in Asian (44%), Black (22%), and Hispanic, Native American and Alaskan Native babies (14%), the Times article stated. In the United States, the number of CF variants tested for falls into a wide range: from the one variant found mostly in White populations in Mississippi (with a 38% Black populace) to 689 variants in Wisconsin.

Callista Images/Image Source/Getty Images

Today’s CF challenges

Beyond refinements in screening instruments and policies that broaden access leading to the earliest possible diagnoses, ongoing research needs include finding treatments for other variants, and caring for adult populations living with treated CF and the disease’s multisystem manifestations. “As people with CF live longer, we need to be very focused on optimized adult medical care for this population,” Marc A. Sala, MD, assistant professor of medicine, Adult CF Program, Northwestern University Feinberg School of Medicine, Chicago, said in an interview. “For example, we need higher vigilance for liver, microvascular, coronary artery disease, and various cancer screenings. We do not know exactly how these will manifest differently from the way they do in non-CF populations, so this is where more work needs to be done.”

Northwestern University Feinberg School of Medicine

Emphasis on monitoring

The authors of “Future therapies for cystic fibrosis” (Allen et al. Nature Communications, 2023 Feb 8), after citing the ongoing transformative change for people with CF since the introduction of CFTR drugs, gave voice to important cautions. “Disease will progress, albeit more slowly, and will be more challenging to monitor. Effective CFTR modulators will likely slow or, at best, halt disease progression, but will not reverse a disease that has already become fixed.” They cited pancreatic destruction in the majority, bronchiectasis, and absence of the vas deferens, with still recurring (although less frequently) pulmonary exacerbations along with chronic infections and persistent airway inflammation. “It is essential that we do not become complacent about disease progression in this population,” the researchers stated. They cautioned also that effective surveillance for infection is critical in asymptomatic patients, emphasizing that it underpins the management of young healthy children with CF who demonstrate disease progression despite a lack of symptoms.

Among the ~90% for whom Trikafta is suitable and approved (those with least one copy of F508del or specific other responsive mutations), improvements include increased percent predicted FEV₁ by 10%-15% or more, decreased exacerbations, and improved quality of life,” Dr. Sala said. “Subsequent ‘real world’ experience shows dramatic reductions in sputum production and decreased frequency of lung transplant.”
 

Mutation agnostic therapy

Unfortunately, CF mutants, outside the population eligible for Trikafta, are prodigious in number and do not fall into just a few major groups. “Furthermore, although CF is a monogenic disease, it has variable phenotypes even for two individuals with the same mutations,” Dr. Sala said. “Current CFTR modulators act on the dysfunctional CFTR protein (either as channel gating potentiators or molecular chaperones to improve misfolding). That leaves about 10% of the CF population, those with little to no protein production (such as in nonsense mutations) ineligible for treatment with CFTR modulators. “The ideal for efficacy and equity, given that some CFTR mutations only exist in a handful of people, would be to develop a ‘mutation agnostic’ strategy — such as with mRNA or gene delivery. Here you could imagine that regardless of the type of mutation, a patient would then be able to receive the technology to increase CFTR channel function,” Dr. Sala said. Many modifiable factors, including host immunity and non-CFTR genes that impact CFTR indirectly, may underlie the fact that one person has a worse trajectory than another. “New therapies may also be found in this area of research,” Dr. Sala said.

Strategies in testing phases

“For patients with class I (nonsense) mutations there is hope that small molecules will be identified that can facilitate premature truncation codon (PTC) read-through and/or impede mRNA decay allowing for clinically relevant levels of functional CFTR,” the researchers noted. While the most extensively developed, ataluren, an oxadiazole, failed in phase 3 trials after initial promise, other ribosomal read-through drugs are in preclinical and early phase clinical trials. Also, early encouraging results support an alternative strategy, engineered transfer RNAs (tRNAs) that introduce an amino acid to an elongating peptide in place of the termination codon.

While these will address specific mutations, DNA or mRNA replacement strategies would be “mutation agnostic,” the researchers stated. The major challenge: delivery to the respiratory epithelium. Approaches currently in early testing include an inhaled aerosolized, lipid-based nanoparticle carrier for mRNA delivery, viral and non-viral DNA transfer, lipid-mediated CFTR gene transfer, pseudotyped lentiviral vector and adeno-associated vector transfer of CFTR DNA.
 

Adult CF care

“Adult CF care in general is a completely new frontier,” Meilinh Thi, DO, director of the adult cystic fibrosis program and assistant professor at University of Texas Health at San Antonio, said in an interview. “It’s fairly new to have separate pediatric and adult CF centers. There’s been a shift,” she said. “We’re encountering diseases in CF that we have not in the past had to deal with: diabetes that has features of both type 1 and type 2, increased colon cancer risk, bone disease, and mental health issues. Also, while pregnancy was previously discouraged for women with CF because of lung disease, now many are giving birth without complications and living normal lives,” Dr. Thi said.

University of Texas Health at San Antonio

“We do encourage our patients to talk to us before becoming pregnant so we can discuss the risk of passing on the gene. And, we do encourage their significant others to get testing. Some patients and their others, however, do decline to get tested,” she added.

The lifetime health issues conferred by CF, Dr. Thi noted, include lung disease with chronic inflammation, infection, respiratory failure (still the most common cause of death), gastrointestinal disorders (including of the pancreas) , colon obstruction and colon cancer, sinus disease, and reproductive system effects. Their permanence, she said, depends on how far their disease has progressed. “So the earlier you can provide these newer therapies — the modulators, for example, or the gene therapy whenever that comes out, then the less damage these organ systems will have, and the patients, we hope, will then do better.”

After Rena Barrow-Wells, an African American mother, fought mightily to prevent a repeat of her experience of two decades earlier when her first child’s cystic fibrosis (CF) took 4 years to diagnose, her story became the subject of a New York Times feature covering disparities in diagnostic CF screening. The article highlighted not only her struggles, but also the utter transformation of the CF landscape since the introduction of small molecule mutation-specific drugs. These drugs restore function to defective CF transmembrane conductance regulator (CFTR) proteins. By the time Ms. Barrow-Wells’ young son was treated, lung and pancreatic scarring were already significant. So when the 39-mutation variant screening test available in Ms. Barrow-Wells’ Lawrenceville, Georgia, clinic turned out negative for CF, her pediatrician told her to stop worrying despite her new son’s inherent genetic risk, telltale salty skin, foul-smelling diapers, and her pleas to test for sweat chloride. It still took 3 months for a confirmed diagnosis and the initiation of treatment.

Current genetic tests, based largely on older clinical trials that enrolled mostly white children, are highly accurate for identifying CF in white babies (95%), but often fail to identify substantial percentages of mutations originating in Africa, Asia, and Latin America. They miss CF in Asian (44%), Black (22%), and Hispanic, Native American and Alaskan Native babies (14%), the Times article stated. In the United States, the number of CF variants tested for falls into a wide range: from the one variant found mostly in White populations in Mississippi (with a 38% Black populace) to 689 variants in Wisconsin.

Callista Images/Image Source/Getty Images

Today’s CF challenges

Beyond refinements in screening instruments and policies that broaden access leading to the earliest possible diagnoses, ongoing research needs include finding treatments for other variants, and caring for adult populations living with treated CF and the disease’s multisystem manifestations. “As people with CF live longer, we need to be very focused on optimized adult medical care for this population,” Marc A. Sala, MD, assistant professor of medicine, Adult CF Program, Northwestern University Feinberg School of Medicine, Chicago, said in an interview. “For example, we need higher vigilance for liver, microvascular, coronary artery disease, and various cancer screenings. We do not know exactly how these will manifest differently from the way they do in non-CF populations, so this is where more work needs to be done.”

Northwestern University Feinberg School of Medicine

Emphasis on monitoring

The authors of “Future therapies for cystic fibrosis” (Allen et al. Nature Communications, 2023 Feb 8), after citing the ongoing transformative change for people with CF since the introduction of CFTR drugs, gave voice to important cautions. “Disease will progress, albeit more slowly, and will be more challenging to monitor. Effective CFTR modulators will likely slow or, at best, halt disease progression, but will not reverse a disease that has already become fixed.” They cited pancreatic destruction in the majority, bronchiectasis, and absence of the vas deferens, with still recurring (although less frequently) pulmonary exacerbations along with chronic infections and persistent airway inflammation. “It is essential that we do not become complacent about disease progression in this population,” the researchers stated. They cautioned also that effective surveillance for infection is critical in asymptomatic patients, emphasizing that it underpins the management of young healthy children with CF who demonstrate disease progression despite a lack of symptoms.

Among the ~90% for whom Trikafta is suitable and approved (those with least one copy of F508del or specific other responsive mutations), improvements include increased percent predicted FEV₁ by 10%-15% or more, decreased exacerbations, and improved quality of life,” Dr. Sala said. “Subsequent ‘real world’ experience shows dramatic reductions in sputum production and decreased frequency of lung transplant.”
 

Mutation agnostic therapy

Unfortunately, CF mutants, outside the population eligible for Trikafta, are prodigious in number and do not fall into just a few major groups. “Furthermore, although CF is a monogenic disease, it has variable phenotypes even for two individuals with the same mutations,” Dr. Sala said. “Current CFTR modulators act on the dysfunctional CFTR protein (either as channel gating potentiators or molecular chaperones to improve misfolding). That leaves about 10% of the CF population, those with little to no protein production (such as in nonsense mutations) ineligible for treatment with CFTR modulators. “The ideal for efficacy and equity, given that some CFTR mutations only exist in a handful of people, would be to develop a ‘mutation agnostic’ strategy — such as with mRNA or gene delivery. Here you could imagine that regardless of the type of mutation, a patient would then be able to receive the technology to increase CFTR channel function,” Dr. Sala said. Many modifiable factors, including host immunity and non-CFTR genes that impact CFTR indirectly, may underlie the fact that one person has a worse trajectory than another. “New therapies may also be found in this area of research,” Dr. Sala said.

Strategies in testing phases

“For patients with class I (nonsense) mutations there is hope that small molecules will be identified that can facilitate premature truncation codon (PTC) read-through and/or impede mRNA decay allowing for clinically relevant levels of functional CFTR,” the researchers noted. While the most extensively developed, ataluren, an oxadiazole, failed in phase 3 trials after initial promise, other ribosomal read-through drugs are in preclinical and early phase clinical trials. Also, early encouraging results support an alternative strategy, engineered transfer RNAs (tRNAs) that introduce an amino acid to an elongating peptide in place of the termination codon.

While these will address specific mutations, DNA or mRNA replacement strategies would be “mutation agnostic,” the researchers stated. The major challenge: delivery to the respiratory epithelium. Approaches currently in early testing include an inhaled aerosolized, lipid-based nanoparticle carrier for mRNA delivery, viral and non-viral DNA transfer, lipid-mediated CFTR gene transfer, pseudotyped lentiviral vector and adeno-associated vector transfer of CFTR DNA.
 

Adult CF care

“Adult CF care in general is a completely new frontier,” Meilinh Thi, DO, director of the adult cystic fibrosis program and assistant professor at University of Texas Health at San Antonio, said in an interview. “It’s fairly new to have separate pediatric and adult CF centers. There’s been a shift,” she said. “We’re encountering diseases in CF that we have not in the past had to deal with: diabetes that has features of both type 1 and type 2, increased colon cancer risk, bone disease, and mental health issues. Also, while pregnancy was previously discouraged for women with CF because of lung disease, now many are giving birth without complications and living normal lives,” Dr. Thi said.

University of Texas Health at San Antonio

“We do encourage our patients to talk to us before becoming pregnant so we can discuss the risk of passing on the gene. And, we do encourage their significant others to get testing. Some patients and their others, however, do decline to get tested,” she added.

The lifetime health issues conferred by CF, Dr. Thi noted, include lung disease with chronic inflammation, infection, respiratory failure (still the most common cause of death), gastrointestinal disorders (including of the pancreas) , colon obstruction and colon cancer, sinus disease, and reproductive system effects. Their permanence, she said, depends on how far their disease has progressed. “So the earlier you can provide these newer therapies — the modulators, for example, or the gene therapy whenever that comes out, then the less damage these organ systems will have, and the patients, we hope, will then do better.”

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The MightySat Medical, an over-the-counter medical fingertip pulse oximeter, has received clearance from the US Food and Drug Administration (FDA) for use without a prescription, according to a press release from manufacturer Masimo.

The device is the first medical fingertip pulse oximeter available directly to consumers without a prescription that includes the same technology used by many hospitals, according to the company.

According to the FDA, home pulse oximeters are currently generally of two classes: hospital-grade prescription devices which have been vetted for accuracy through clinical trials, and over-the-counter devices which are sold direct to consumers but often estimate oxygen saturation. FDA communication on pulse oximeter accuracy states "OTC oximeters that are sold as either general wellness or sporting/aviation products are not intended for medical purposes, so they do not undergo FDA review."

Pulse oximeter use is important for patients diagnosed with breathing problems or lung diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, flu, pneumonia, or COVID-19 to collect accurate data on arterial blood oxygen saturation that they can share with their healthcare providers, according to the company. Patients with cardiac conditions, including pulmonary hypertension and heart failure may also benefit from pulse oximeter monitoring.

However, challenges of pulse oximeter use include measuring accuracy when patients are moving, measuring patients with poor circulation, and measuring patients with cool, thick, or darker skin. The MightySat Medical is designed to provide reliable measures of oxygen saturation and pulse rate across all patient groups, the manufacturers wrote in the press release.

Asked for additional comment, Diego J. Maselli, MD, FCCP, Professor and Chief in the division of Pulmonary Diseases and Critical Care at UT Health at San Antonio, noted, "Over the past decades, there has been an increased interest in home monitoring of medical conditions, particulrly with the development of more portable and accessible technology."

"This was heightended by the COVID-19 pandemic where telemedicine was frequently required as a means of delivering care," Dr. Maselli continued. "One of the important characteristics to monitor was the oxgen saturation in patients that had an active COVID-19 infection as it would dictate management and was part of the protocol for monitoring the clinical course of infection. Because of this need, many companies developed portable pulse oximeters for home use. This resulted in widespread use of pulse oximeters at home and other places outside clinic or hospital."

Other over-the-counter pulse oximeters that are not cleared by the FDA may create confusion among patients about the accuracy of their measurements, according to the company.

Dr. Maselli also commented that pulse oximeters' value can vary. "Unfortunately, these devices vary in quality and reliability and patients may not be fully aware of this. Most recently, the FDA approved a hospital-grade pulse oximeter that requires no prescription. This device may provide a more accurate reading in a wide range of clinical situations outside the healthcare setting. Patients should be aware that there are different grades of pulse oximeter before selecting one for home use. In addition, patients should work closely with their providers to better select the monitoring modaility that best fits their clinical situation," he said.

MightySat Medical is indicated for individuals aged 18 years and older who are well or poorly perfused under no motion conditions and is not intended as a diagnostic or screening tool for lung disease, according to the release. Treatment decisions based on data from the device should be made only in consultation with a healthcare provider, the company said. Dr. Maselli serves as a member of the CHEST Physician editorial board.

The FDA’s website offers further guidance related to at-home pulse oximeter use, with recommendations and limitations, as well as information on initiatives to ensure accurate and equitable pulse oximetry for all patients.

A version of this article appeared on Medscape.com.

The MightySat Medical, an over-the-counter medical fingertip pulse oximeter, has received clearance from the US Food and Drug Administration (FDA) for use without a prescription, according to a press release from manufacturer Masimo.

The device is the first medical fingertip pulse oximeter available directly to consumers without a prescription that includes the same technology used by many hospitals, according to the company.

According to the FDA, home pulse oximeters are currently generally of two classes: hospital-grade prescription devices which have been vetted for accuracy through clinical trials, and over-the-counter devices which are sold direct to consumers but often estimate oxygen saturation. FDA communication on pulse oximeter accuracy states "OTC oximeters that are sold as either general wellness or sporting/aviation products are not intended for medical purposes, so they do not undergo FDA review."

Pulse oximeter use is important for patients diagnosed with breathing problems or lung diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, flu, pneumonia, or COVID-19 to collect accurate data on arterial blood oxygen saturation that they can share with their healthcare providers, according to the company. Patients with cardiac conditions, including pulmonary hypertension and heart failure may also benefit from pulse oximeter monitoring.

However, challenges of pulse oximeter use include measuring accuracy when patients are moving, measuring patients with poor circulation, and measuring patients with cool, thick, or darker skin. The MightySat Medical is designed to provide reliable measures of oxygen saturation and pulse rate across all patient groups, the manufacturers wrote in the press release.

Asked for additional comment, Diego J. Maselli, MD, FCCP, Professor and Chief in the division of Pulmonary Diseases and Critical Care at UT Health at San Antonio, noted, "Over the past decades, there has been an increased interest in home monitoring of medical conditions, particulrly with the development of more portable and accessible technology."

"This was heightended by the COVID-19 pandemic where telemedicine was frequently required as a means of delivering care," Dr. Maselli continued. "One of the important characteristics to monitor was the oxgen saturation in patients that had an active COVID-19 infection as it would dictate management and was part of the protocol for monitoring the clinical course of infection. Because of this need, many companies developed portable pulse oximeters for home use. This resulted in widespread use of pulse oximeters at home and other places outside clinic or hospital."

Other over-the-counter pulse oximeters that are not cleared by the FDA may create confusion among patients about the accuracy of their measurements, according to the company.

Dr. Maselli also commented that pulse oximeters' value can vary. "Unfortunately, these devices vary in quality and reliability and patients may not be fully aware of this. Most recently, the FDA approved a hospital-grade pulse oximeter that requires no prescription. This device may provide a more accurate reading in a wide range of clinical situations outside the healthcare setting. Patients should be aware that there are different grades of pulse oximeter before selecting one for home use. In addition, patients should work closely with their providers to better select the monitoring modaility that best fits their clinical situation," he said.

MightySat Medical is indicated for individuals aged 18 years and older who are well or poorly perfused under no motion conditions and is not intended as a diagnostic or screening tool for lung disease, according to the release. Treatment decisions based on data from the device should be made only in consultation with a healthcare provider, the company said. Dr. Maselli serves as a member of the CHEST Physician editorial board.

The FDA’s website offers further guidance related to at-home pulse oximeter use, with recommendations and limitations, as well as information on initiatives to ensure accurate and equitable pulse oximetry for all patients.

A version of this article appeared on Medscape.com.

The MightySat Medical, an over-the-counter medical fingertip pulse oximeter, has received clearance from the US Food and Drug Administration (FDA) for use without a prescription, according to a press release from manufacturer Masimo.

The device is the first medical fingertip pulse oximeter available directly to consumers without a prescription that includes the same technology used by many hospitals, according to the company.

According to the FDA, home pulse oximeters are currently generally of two classes: hospital-grade prescription devices which have been vetted for accuracy through clinical trials, and over-the-counter devices which are sold direct to consumers but often estimate oxygen saturation. FDA communication on pulse oximeter accuracy states "OTC oximeters that are sold as either general wellness or sporting/aviation products are not intended for medical purposes, so they do not undergo FDA review."

Pulse oximeter use is important for patients diagnosed with breathing problems or lung diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, flu, pneumonia, or COVID-19 to collect accurate data on arterial blood oxygen saturation that they can share with their healthcare providers, according to the company. Patients with cardiac conditions, including pulmonary hypertension and heart failure may also benefit from pulse oximeter monitoring.

However, challenges of pulse oximeter use include measuring accuracy when patients are moving, measuring patients with poor circulation, and measuring patients with cool, thick, or darker skin. The MightySat Medical is designed to provide reliable measures of oxygen saturation and pulse rate across all patient groups, the manufacturers wrote in the press release.

Asked for additional comment, Diego J. Maselli, MD, FCCP, Professor and Chief in the division of Pulmonary Diseases and Critical Care at UT Health at San Antonio, noted, "Over the past decades, there has been an increased interest in home monitoring of medical conditions, particulrly with the development of more portable and accessible technology."

"This was heightended by the COVID-19 pandemic where telemedicine was frequently required as a means of delivering care," Dr. Maselli continued. "One of the important characteristics to monitor was the oxgen saturation in patients that had an active COVID-19 infection as it would dictate management and was part of the protocol for monitoring the clinical course of infection. Because of this need, many companies developed portable pulse oximeters for home use. This resulted in widespread use of pulse oximeters at home and other places outside clinic or hospital."

Other over-the-counter pulse oximeters that are not cleared by the FDA may create confusion among patients about the accuracy of their measurements, according to the company.

Dr. Maselli also commented that pulse oximeters' value can vary. "Unfortunately, these devices vary in quality and reliability and patients may not be fully aware of this. Most recently, the FDA approved a hospital-grade pulse oximeter that requires no prescription. This device may provide a more accurate reading in a wide range of clinical situations outside the healthcare setting. Patients should be aware that there are different grades of pulse oximeter before selecting one for home use. In addition, patients should work closely with their providers to better select the monitoring modaility that best fits their clinical situation," he said.

MightySat Medical is indicated for individuals aged 18 years and older who are well or poorly perfused under no motion conditions and is not intended as a diagnostic or screening tool for lung disease, according to the release. Treatment decisions based on data from the device should be made only in consultation with a healthcare provider, the company said. Dr. Maselli serves as a member of the CHEST Physician editorial board.

The FDA’s website offers further guidance related to at-home pulse oximeter use, with recommendations and limitations, as well as information on initiatives to ensure accurate and equitable pulse oximetry for all patients.

A version of this article appeared on Medscape.com.