Marie M. Budev, DO, MPH

A 66-year-old white man presents with a 1-month history of two nontender, nonpruritic skin lesions on his leg 3 weeks after undergoing bilateral lung transplantation for idiopathic pulmonary fibrosis (Figure 1). Except for transient lymphopenia, the postoperative course has been uneventful, with no episodes of rejection. Immunosuppressive drugs include tacrolimus (Prograf) and steroids. He has a history of insulin-dependent diabetes mellitus, and no history of significant trauma to his legs. Other than the skin lesions, he feels well and has no systemic symptoms. He has no history of iron overload or deferoxamine (Desferal) therapy.

Q: What is the probable diagnosis?

• Kaposi sarcoma
• Majocchi (trichophytic) granuloma
• Staphylococcus aureus furunculosis
• Primary cutaneous mucormycosis
• Disseminated zoster

A: This patient has primary cutaneous mucormycosis. Microscopic examination of the skin biopsy showed suppurative granulomatous inflammation with numerous nonseptated, branching fungal hyphae (Figure 2). A fungal culture grew Absidia species. No evidence of disseminated disease was found on computed tomography of the brain, paranasal sinuses, chest, abdomen, and pelvis. Histologic studies and cultures taken from both native and transplanted lungs were negative for fungi.

CAUSES AND RISK FACTORS

Mucormycosis is an invasive infection caused by fungi of a variety of genera (Rhizopus, Rhizomucor, Mucor, Absidia, Apophysomyces, Cunninghamella, Saksenaea, Conidiobolus, and Basidiobolus species) belonging to the class Zygomycetes in the order Mucorales. These ubiquitous environmental fungi have been found widely distributed in hospital sources, having been cultured from plaster casts,¹ tongue depressors,² cloth tapes for securing endotracheal tubes,³ peritoneal dialysis catheters,⁴ surgical wounds,⁵ contaminated dressings, needles, and intravenous catheters.⁶

These fungi rarely cause disease in healthy people, but patients with certain risk factors may develop disseminated disease, in which the death rate is high.⁶ Risk factors include diabetes mellitus, renal failure, trauma, burns, malnutrition, solid organ transplantation, hematologic malignancies, use of immunosuppressive drugs (eg, chemotherapeutic agents, corticosteroids, cyclosporine, methotrexate, infliximab [Remicade]⁷), and iron overload and iron-chelating therapy with deferoxamine. ⁸ Patients such as ours—an organ transplant recipient with concomitant diabetes mellitus—are highly susceptible to this infection.

DIAGNOSIS

The clinical presentation of mucormycosis can be rhino-orbitocerebral (most common),⁹ pulmonary, primary cutaneous, gastrointestinal, cardiac, or disseminated infection.⁶ Primary cutaneous mucormycosis occurs from fungal inoculation of the dermis. Small areas of trauma may be all that is needed for this inoculation to occur.

The initial lesion may be an erythematous patch, plaque, or nodule that may subsequently ulcerate and become gangrenous or necrotic.¹⁰

The differential diagnosis of new cutaneous nodules in an immunocompromised patient includes a wide variety of infections, such as ecthyma gangrenosum caused by Pseudomonas or Candida species, herpes simplex virus infection, cryptococcal infection, phaeohyphomycosis, and cutaneous aspergillosis.

Because the morphology of cutaneous mucormycosis is not distinctive, and because we need to cast our net wide for the numerous, potentially lethal diagnostic possibilities in an immunosuppressed patient, it is crucial that we have a low threshold for prompt biopsy to establish the diagnosis and initiate definitive treatment. While skin biopsy for microscopy can suggest certain fungi, the exact diagnosis is confirmed by a fungal culture of a biopsy specimen.

TREATMENT

Localized soft tissue infection is more amenable to therapy and therefore carries a better prognosis than visceral or disseminated disease.

The best treatment outcomes of primary cutaneous mucormycosis are achieved with both complete excision and debridement of necrotic tissue and systemic antifungal therapy. Amphotericin B in conventional form (Fungizone) and liposomal form (AmBisome) and posaconazole (Noxafil)^11–12 are effective.

Paradoxically, in contrast to deferoxamine, other iron chelators such as deferiprone (Ferriprox, not available in the United States) and deferasirox (Exjade), which do not supply iron to the fungus, had been shown to be effective against Zygomycetes in in vitro and animal models. The role of iron chelators as adjunctive therapy for mucormycosis needs further investigation.⁸

Primary cutaneous mucormycosis may become a disseminated infection. Therefore, one should have a high index of suspicion. When a transplant recipient develops a cutaneous plaque or nodule, biopsy should be performed promptly. Failure to do so can increase the risk of morbidity and death.

A 66-year-old white man presents with a 1-month history of two nontender, nonpruritic skin lesions on his leg 3 weeks after undergoing bilateral lung transplantation for idiopathic pulmonary fibrosis (Figure 1). Except for transient lymphopenia, the postoperative course has been uneventful, with no episodes of rejection. Immunosuppressive drugs include tacrolimus (Prograf) and steroids. He has a history of insulin-dependent diabetes mellitus, and no history of significant trauma to his legs. Other than the skin lesions, he feels well and has no systemic symptoms. He has no history of iron overload or deferoxamine (Desferal) therapy.

Q: What is the probable diagnosis?

• Kaposi sarcoma
• Majocchi (trichophytic) granuloma
• Staphylococcus aureus furunculosis
• Primary cutaneous mucormycosis
• Disseminated zoster

A: This patient has primary cutaneous mucormycosis. Microscopic examination of the skin biopsy showed suppurative granulomatous inflammation with numerous nonseptated, branching fungal hyphae (Figure 2). A fungal culture grew Absidia species. No evidence of disseminated disease was found on computed tomography of the brain, paranasal sinuses, chest, abdomen, and pelvis. Histologic studies and cultures taken from both native and transplanted lungs were negative for fungi.

CAUSES AND RISK FACTORS

Mucormycosis is an invasive infection caused by fungi of a variety of genera (Rhizopus, Rhizomucor, Mucor, Absidia, Apophysomyces, Cunninghamella, Saksenaea, Conidiobolus, and Basidiobolus species) belonging to the class Zygomycetes in the order Mucorales. These ubiquitous environmental fungi have been found widely distributed in hospital sources, having been cultured from plaster casts,¹ tongue depressors,² cloth tapes for securing endotracheal tubes,³ peritoneal dialysis catheters,⁴ surgical wounds,⁵ contaminated dressings, needles, and intravenous catheters.⁶

These fungi rarely cause disease in healthy people, but patients with certain risk factors may develop disseminated disease, in which the death rate is high.⁶ Risk factors include diabetes mellitus, renal failure, trauma, burns, malnutrition, solid organ transplantation, hematologic malignancies, use of immunosuppressive drugs (eg, chemotherapeutic agents, corticosteroids, cyclosporine, methotrexate, infliximab [Remicade]⁷), and iron overload and iron-chelating therapy with deferoxamine. ⁸ Patients such as ours—an organ transplant recipient with concomitant diabetes mellitus—are highly susceptible to this infection.

DIAGNOSIS

The clinical presentation of mucormycosis can be rhino-orbitocerebral (most common),⁹ pulmonary, primary cutaneous, gastrointestinal, cardiac, or disseminated infection.⁶ Primary cutaneous mucormycosis occurs from fungal inoculation of the dermis. Small areas of trauma may be all that is needed for this inoculation to occur.

The initial lesion may be an erythematous patch, plaque, or nodule that may subsequently ulcerate and become gangrenous or necrotic.¹⁰

The differential diagnosis of new cutaneous nodules in an immunocompromised patient includes a wide variety of infections, such as ecthyma gangrenosum caused by Pseudomonas or Candida species, herpes simplex virus infection, cryptococcal infection, phaeohyphomycosis, and cutaneous aspergillosis.

Because the morphology of cutaneous mucormycosis is not distinctive, and because we need to cast our net wide for the numerous, potentially lethal diagnostic possibilities in an immunosuppressed patient, it is crucial that we have a low threshold for prompt biopsy to establish the diagnosis and initiate definitive treatment. While skin biopsy for microscopy can suggest certain fungi, the exact diagnosis is confirmed by a fungal culture of a biopsy specimen.

TREATMENT

Localized soft tissue infection is more amenable to therapy and therefore carries a better prognosis than visceral or disseminated disease.

The best treatment outcomes of primary cutaneous mucormycosis are achieved with both complete excision and debridement of necrotic tissue and systemic antifungal therapy. Amphotericin B in conventional form (Fungizone) and liposomal form (AmBisome) and posaconazole (Noxafil)^11–12 are effective.

Paradoxically, in contrast to deferoxamine, other iron chelators such as deferiprone (Ferriprox, not available in the United States) and deferasirox (Exjade), which do not supply iron to the fungus, had been shown to be effective against Zygomycetes in in vitro and animal models. The role of iron chelators as adjunctive therapy for mucormycosis needs further investigation.⁸

Primary cutaneous mucormycosis may become a disseminated infection. Therefore, one should have a high index of suspicion. When a transplant recipient develops a cutaneous plaque or nodule, biopsy should be performed promptly. Failure to do so can increase the risk of morbidity and death.

A 66-year-old white man presents with a 1-month history of two nontender, nonpruritic skin lesions on his leg 3 weeks after undergoing bilateral lung transplantation for idiopathic pulmonary fibrosis (Figure 1). Except for transient lymphopenia, the postoperative course has been uneventful, with no episodes of rejection. Immunosuppressive drugs include tacrolimus (Prograf) and steroids. He has a history of insulin-dependent diabetes mellitus, and no history of significant trauma to his legs. Other than the skin lesions, he feels well and has no systemic symptoms. He has no history of iron overload or deferoxamine (Desferal) therapy.

Q: What is the probable diagnosis?

• Kaposi sarcoma
• Majocchi (trichophytic) granuloma
• Staphylococcus aureus furunculosis
• Primary cutaneous mucormycosis
• Disseminated zoster

A: This patient has primary cutaneous mucormycosis. Microscopic examination of the skin biopsy showed suppurative granulomatous inflammation with numerous nonseptated, branching fungal hyphae (Figure 2). A fungal culture grew Absidia species. No evidence of disseminated disease was found on computed tomography of the brain, paranasal sinuses, chest, abdomen, and pelvis. Histologic studies and cultures taken from both native and transplanted lungs were negative for fungi.

CAUSES AND RISK FACTORS

Mucormycosis is an invasive infection caused by fungi of a variety of genera (Rhizopus, Rhizomucor, Mucor, Absidia, Apophysomyces, Cunninghamella, Saksenaea, Conidiobolus, and Basidiobolus species) belonging to the class Zygomycetes in the order Mucorales. These ubiquitous environmental fungi have been found widely distributed in hospital sources, having been cultured from plaster casts,¹ tongue depressors,² cloth tapes for securing endotracheal tubes,³ peritoneal dialysis catheters,⁴ surgical wounds,⁵ contaminated dressings, needles, and intravenous catheters.⁶

These fungi rarely cause disease in healthy people, but patients with certain risk factors may develop disseminated disease, in which the death rate is high.⁶ Risk factors include diabetes mellitus, renal failure, trauma, burns, malnutrition, solid organ transplantation, hematologic malignancies, use of immunosuppressive drugs (eg, chemotherapeutic agents, corticosteroids, cyclosporine, methotrexate, infliximab [Remicade]⁷), and iron overload and iron-chelating therapy with deferoxamine. ⁸ Patients such as ours—an organ transplant recipient with concomitant diabetes mellitus—are highly susceptible to this infection.

DIAGNOSIS

The clinical presentation of mucormycosis can be rhino-orbitocerebral (most common),⁹ pulmonary, primary cutaneous, gastrointestinal, cardiac, or disseminated infection.⁶ Primary cutaneous mucormycosis occurs from fungal inoculation of the dermis. Small areas of trauma may be all that is needed for this inoculation to occur.

The initial lesion may be an erythematous patch, plaque, or nodule that may subsequently ulcerate and become gangrenous or necrotic.¹⁰

The differential diagnosis of new cutaneous nodules in an immunocompromised patient includes a wide variety of infections, such as ecthyma gangrenosum caused by Pseudomonas or Candida species, herpes simplex virus infection, cryptococcal infection, phaeohyphomycosis, and cutaneous aspergillosis.

Because the morphology of cutaneous mucormycosis is not distinctive, and because we need to cast our net wide for the numerous, potentially lethal diagnostic possibilities in an immunosuppressed patient, it is crucial that we have a low threshold for prompt biopsy to establish the diagnosis and initiate definitive treatment. While skin biopsy for microscopy can suggest certain fungi, the exact diagnosis is confirmed by a fungal culture of a biopsy specimen.

TREATMENT

Localized soft tissue infection is more amenable to therapy and therefore carries a better prognosis than visceral or disseminated disease.

The best treatment outcomes of primary cutaneous mucormycosis are achieved with both complete excision and debridement of necrotic tissue and systemic antifungal therapy. Amphotericin B in conventional form (Fungizone) and liposomal form (AmBisome) and posaconazole (Noxafil)^11–12 are effective.

Paradoxically, in contrast to deferoxamine, other iron chelators such as deferiprone (Ferriprox, not available in the United States) and deferasirox (Exjade), which do not supply iron to the fungus, had been shown to be effective against Zygomycetes in in vitro and animal models. The role of iron chelators as adjunctive therapy for mucormycosis needs further investigation.⁸

Primary cutaneous mucormycosis may become a disseminated infection. Therefore, one should have a high index of suspicion. When a transplant recipient develops a cutaneous plaque or nodule, biopsy should be performed promptly. Failure to do so can increase the risk of morbidity and death.

Yes. In selected patients with hypercapnic respiratory failure due to an acute exacerbation of chronic obstructive pulmonary disease (COPD), noninvasive positive pressure ventilation (NIPPV) is an effective adjunct to usual medical therapy. In controlled trials, it reduced the need for endotracheal intubation, the length of hospital stay, and the risk of death.

Acute COPD exacerbations are responsible for more than 500,000 hospitalizations yearly in the United States, and 6% to 34% of patients die.¹

Many patients need invasive ventilatory assistance via an endotracheal tube, but such therapy puts the patient at risk of ventilator-associated pneumonia, pneumothorax, and tracheal stenosis.

WHAT IS NONINVASIVE POSITIVE PRESSURE VENTILATION?

With NIPPV, the patient wears a tightly fitting nasal or full facial mask, avoiding the need for an endotracheal tube, laryngeal mask, or tracheostomy (Figure 1).² The mask can be connected to a standard mechanical ventilator or, more commonly, to a continuous positive airway pressure or bi-level airway pressure unit. NIPPV has been used with variable success in a variety of conditions, including COPD exacerbations,^3–6 acute cardiogenic pulmonary edema,⁷ hypoxemic respiratory failure,⁸ and ventilator weaning.⁹

WHY IS IT BENEFICIAL?

Several mechanisms may explain why noninvasive positive pressure ventilation is beneficial in acute exacerbations of COPD.

Patients with decompensated respiratory failure lack sufficient alveolar ventilation, owing to abnormal respiratory mechanics and inspiratory muscle fatigue.¹⁰ For these patients, breathing faster does not fully compensate. Noninvasive positive pressure ventilation partially counteracts these factors by providing a larger tidal volume with the same inspiratory effort.^10,11

Additionally, this treatment can decrease the work of breathing by partially overcoming auto-PEEP (positive end-expiratory pressure) in certain situations.² Auto-PEEP is pressure greater than the atmospheric pressure remaining in the alveoli at the end of exhalation.¹² This condition is related to limited expiratory flow and is common in those with severe COPD. Noninvasive positive pressure ventilation decreases the pressure difference between the atmosphere and the alveoli, thereby reducing the inspiratory force needed for initiation of inspiratory effort, which may reduce the work of breathing. However, caution should be used when using this therapy in tachypneic patients, in whom NIPPV may not fully overcome the auto-PEEP.

WHAT STUDIES SHOWED

Several randomized trials have shown NIPPV to be beneficial in acute hypercapnic COPD exacerbations. A recent meta-analysis of eight studies¹³ showed that, compared with usual care alone, this therapy was associated with:

• A lower mortality rate (relative risk 0.41; 95% confidence interval [CI] 0.26–0.64)
• Less need for endotracheal intubation (relative risk 0.42; 95% CI 0.31–0.59)
• A lower rate of treatment failure (relative risk 0.51; 95% CI 0.38–0.67)
• Greater improvements in the 1-hour post-treatment pH and PaCO₂ levels
• A lower respiratory rate
• A shorter length of stay in the hospital.

 

WHICH PATIENTS SHOULD RECEIVE IT?

Consensus groups have offered guidelines for deciding who should receive NIPPV (Table 1).^14–16 Patients who benefit the most include those who have moderate to severe dyspnea, tachypnea, and hypercarbia and whose pH is 7.25 to 7.35. Of importance, if this treatment is appropriate it should be started without delay, as studies have shown a higher success rate when it is applied early.¹⁷

NIPPV is not suitable for all patients with hypercapnic respiratory failure. It should not be substituted for endotracheal intubation and mechanical ventilation if they are indicated, eg, in patients who are medically unstable because of hypotension, sepsis, hypoxia, or other life-threatening systemic illness. In addition, those who cannot protect the airway, who have had a worsening in mental status, or who have excessive secretions should not undergo NIPPV because they have a high risk of aspiration. Factors that predict that this therapy will fail include an Acute Physiology and Chronic Health Evaluation (APACHE) score of 29 or higher, a respiratory rate of 30 or higher, and a pH lower than 7.25 after 2 hours of this therapy.¹⁵

GENERAL WARD OR INTENSIVE CARE UNIT?

Mild to moderate COPD exacerbations (in which the pH is 7.30 or higher) can be effectively treated with NIPPV in a general ward if the staff has appropriate expertise.^5,18 Keeping the patient in a general ward reduces cost and provides a favorable outcome in selected patients.^5,19 However, if the patient’s hemodynamic or mental status deteriorates or if gas exchange, pH, respiratory rate, or dyspnea fail to improve, he or she should be transferred to an intensive care unit and endotracheal intubation should be considered.¹⁸ The use of NIPPV in general wards should always be approached with caution and should never be attempted without adequate patient supervision and an experienced respiratory therapy team.

TAKE-HOME MESSAGE

NIPPV has been shown to be an effective adjunct in the treatment of acute hypercapnic respiratory failure secondary to a COPD exacerbation, reducing the need for endotracheal intubation, the length of hospital stay, and the mortality rate. On the basis of controlled trials, NIPPV is now considered the ventilatory therapy of choice in selected patients with this condition. However, it should not be used as a substitute for intubation and mechanical ventilation if these are needed or if the patient is at risk of aspiration.

Yes. In selected patients with hypercapnic respiratory failure due to an acute exacerbation of chronic obstructive pulmonary disease (COPD), noninvasive positive pressure ventilation (NIPPV) is an effective adjunct to usual medical therapy. In controlled trials, it reduced the need for endotracheal intubation, the length of hospital stay, and the risk of death.

Acute COPD exacerbations are responsible for more than 500,000 hospitalizations yearly in the United States, and 6% to 34% of patients die.¹

Many patients need invasive ventilatory assistance via an endotracheal tube, but such therapy puts the patient at risk of ventilator-associated pneumonia, pneumothorax, and tracheal stenosis.

WHAT IS NONINVASIVE POSITIVE PRESSURE VENTILATION?

With NIPPV, the patient wears a tightly fitting nasal or full facial mask, avoiding the need for an endotracheal tube, laryngeal mask, or tracheostomy (Figure 1).² The mask can be connected to a standard mechanical ventilator or, more commonly, to a continuous positive airway pressure or bi-level airway pressure unit. NIPPV has been used with variable success in a variety of conditions, including COPD exacerbations,^3–6 acute cardiogenic pulmonary edema,⁷ hypoxemic respiratory failure,⁸ and ventilator weaning.⁹

WHY IS IT BENEFICIAL?

Several mechanisms may explain why noninvasive positive pressure ventilation is beneficial in acute exacerbations of COPD.

Patients with decompensated respiratory failure lack sufficient alveolar ventilation, owing to abnormal respiratory mechanics and inspiratory muscle fatigue.¹⁰ For these patients, breathing faster does not fully compensate. Noninvasive positive pressure ventilation partially counteracts these factors by providing a larger tidal volume with the same inspiratory effort.^10,11

Additionally, this treatment can decrease the work of breathing by partially overcoming auto-PEEP (positive end-expiratory pressure) in certain situations.² Auto-PEEP is pressure greater than the atmospheric pressure remaining in the alveoli at the end of exhalation.¹² This condition is related to limited expiratory flow and is common in those with severe COPD. Noninvasive positive pressure ventilation decreases the pressure difference between the atmosphere and the alveoli, thereby reducing the inspiratory force needed for initiation of inspiratory effort, which may reduce the work of breathing. However, caution should be used when using this therapy in tachypneic patients, in whom NIPPV may not fully overcome the auto-PEEP.

WHAT STUDIES SHOWED

Several randomized trials have shown NIPPV to be beneficial in acute hypercapnic COPD exacerbations. A recent meta-analysis of eight studies¹³ showed that, compared with usual care alone, this therapy was associated with:

• A lower mortality rate (relative risk 0.41; 95% confidence interval [CI] 0.26–0.64)
• Less need for endotracheal intubation (relative risk 0.42; 95% CI 0.31–0.59)
• A lower rate of treatment failure (relative risk 0.51; 95% CI 0.38–0.67)
• Greater improvements in the 1-hour post-treatment pH and PaCO₂ levels
• A lower respiratory rate
• A shorter length of stay in the hospital.

 

WHICH PATIENTS SHOULD RECEIVE IT?

Consensus groups have offered guidelines for deciding who should receive NIPPV (Table 1).^14–16 Patients who benefit the most include those who have moderate to severe dyspnea, tachypnea, and hypercarbia and whose pH is 7.25 to 7.35. Of importance, if this treatment is appropriate it should be started without delay, as studies have shown a higher success rate when it is applied early.¹⁷

NIPPV is not suitable for all patients with hypercapnic respiratory failure. It should not be substituted for endotracheal intubation and mechanical ventilation if they are indicated, eg, in patients who are medically unstable because of hypotension, sepsis, hypoxia, or other life-threatening systemic illness. In addition, those who cannot protect the airway, who have had a worsening in mental status, or who have excessive secretions should not undergo NIPPV because they have a high risk of aspiration. Factors that predict that this therapy will fail include an Acute Physiology and Chronic Health Evaluation (APACHE) score of 29 or higher, a respiratory rate of 30 or higher, and a pH lower than 7.25 after 2 hours of this therapy.¹⁵

GENERAL WARD OR INTENSIVE CARE UNIT?

Mild to moderate COPD exacerbations (in which the pH is 7.30 or higher) can be effectively treated with NIPPV in a general ward if the staff has appropriate expertise.^5,18 Keeping the patient in a general ward reduces cost and provides a favorable outcome in selected patients.^5,19 However, if the patient’s hemodynamic or mental status deteriorates or if gas exchange, pH, respiratory rate, or dyspnea fail to improve, he or she should be transferred to an intensive care unit and endotracheal intubation should be considered.¹⁸ The use of NIPPV in general wards should always be approached with caution and should never be attempted without adequate patient supervision and an experienced respiratory therapy team.

TAKE-HOME MESSAGE

NIPPV has been shown to be an effective adjunct in the treatment of acute hypercapnic respiratory failure secondary to a COPD exacerbation, reducing the need for endotracheal intubation, the length of hospital stay, and the mortality rate. On the basis of controlled trials, NIPPV is now considered the ventilatory therapy of choice in selected patients with this condition. However, it should not be used as a substitute for intubation and mechanical ventilation if these are needed or if the patient is at risk of aspiration.

Yes. In selected patients with hypercapnic respiratory failure due to an acute exacerbation of chronic obstructive pulmonary disease (COPD), noninvasive positive pressure ventilation (NIPPV) is an effective adjunct to usual medical therapy. In controlled trials, it reduced the need for endotracheal intubation, the length of hospital stay, and the risk of death.

Acute COPD exacerbations are responsible for more than 500,000 hospitalizations yearly in the United States, and 6% to 34% of patients die.¹

Many patients need invasive ventilatory assistance via an endotracheal tube, but such therapy puts the patient at risk of ventilator-associated pneumonia, pneumothorax, and tracheal stenosis.

WHAT IS NONINVASIVE POSITIVE PRESSURE VENTILATION?

With NIPPV, the patient wears a tightly fitting nasal or full facial mask, avoiding the need for an endotracheal tube, laryngeal mask, or tracheostomy (Figure 1).² The mask can be connected to a standard mechanical ventilator or, more commonly, to a continuous positive airway pressure or bi-level airway pressure unit. NIPPV has been used with variable success in a variety of conditions, including COPD exacerbations,^3–6 acute cardiogenic pulmonary edema,⁷ hypoxemic respiratory failure,⁸ and ventilator weaning.⁹

WHY IS IT BENEFICIAL?

Several mechanisms may explain why noninvasive positive pressure ventilation is beneficial in acute exacerbations of COPD.

Patients with decompensated respiratory failure lack sufficient alveolar ventilation, owing to abnormal respiratory mechanics and inspiratory muscle fatigue.¹⁰ For these patients, breathing faster does not fully compensate. Noninvasive positive pressure ventilation partially counteracts these factors by providing a larger tidal volume with the same inspiratory effort.^10,11

Additionally, this treatment can decrease the work of breathing by partially overcoming auto-PEEP (positive end-expiratory pressure) in certain situations.² Auto-PEEP is pressure greater than the atmospheric pressure remaining in the alveoli at the end of exhalation.¹² This condition is related to limited expiratory flow and is common in those with severe COPD. Noninvasive positive pressure ventilation decreases the pressure difference between the atmosphere and the alveoli, thereby reducing the inspiratory force needed for initiation of inspiratory effort, which may reduce the work of breathing. However, caution should be used when using this therapy in tachypneic patients, in whom NIPPV may not fully overcome the auto-PEEP.

WHAT STUDIES SHOWED

Several randomized trials have shown NIPPV to be beneficial in acute hypercapnic COPD exacerbations. A recent meta-analysis of eight studies¹³ showed that, compared with usual care alone, this therapy was associated with:

• A lower mortality rate (relative risk 0.41; 95% confidence interval [CI] 0.26–0.64)
• Less need for endotracheal intubation (relative risk 0.42; 95% CI 0.31–0.59)
• A lower rate of treatment failure (relative risk 0.51; 95% CI 0.38–0.67)
• Greater improvements in the 1-hour post-treatment pH and PaCO₂ levels
• A lower respiratory rate
• A shorter length of stay in the hospital.

 

WHICH PATIENTS SHOULD RECEIVE IT?

Consensus groups have offered guidelines for deciding who should receive NIPPV (Table 1).^14–16 Patients who benefit the most include those who have moderate to severe dyspnea, tachypnea, and hypercarbia and whose pH is 7.25 to 7.35. Of importance, if this treatment is appropriate it should be started without delay, as studies have shown a higher success rate when it is applied early.¹⁷

NIPPV is not suitable for all patients with hypercapnic respiratory failure. It should not be substituted for endotracheal intubation and mechanical ventilation if they are indicated, eg, in patients who are medically unstable because of hypotension, sepsis, hypoxia, or other life-threatening systemic illness. In addition, those who cannot protect the airway, who have had a worsening in mental status, or who have excessive secretions should not undergo NIPPV because they have a high risk of aspiration. Factors that predict that this therapy will fail include an Acute Physiology and Chronic Health Evaluation (APACHE) score of 29 or higher, a respiratory rate of 30 or higher, and a pH lower than 7.25 after 2 hours of this therapy.¹⁵

GENERAL WARD OR INTENSIVE CARE UNIT?

Mild to moderate COPD exacerbations (in which the pH is 7.30 or higher) can be effectively treated with NIPPV in a general ward if the staff has appropriate expertise.^5,18 Keeping the patient in a general ward reduces cost and provides a favorable outcome in selected patients.^5,19 However, if the patient’s hemodynamic or mental status deteriorates or if gas exchange, pH, respiratory rate, or dyspnea fail to improve, he or she should be transferred to an intensive care unit and endotracheal intubation should be considered.¹⁸ The use of NIPPV in general wards should always be approached with caution and should never be attempted without adequate patient supervision and an experienced respiratory therapy team.

TAKE-HOME MESSAGE

NIPPV has been shown to be an effective adjunct in the treatment of acute hypercapnic respiratory failure secondary to a COPD exacerbation, reducing the need for endotracheal intubation, the length of hospital stay, and the mortality rate. On the basis of controlled trials, NIPPV is now considered the ventilatory therapy of choice in selected patients with this condition. However, it should not be used as a substitute for intubation and mechanical ventilation if these are needed or if the patient is at risk of aspiration.

In detecting and evaluating pleural effusion, technology has not replaced clinical skills. Yet, despite centuries of lore, data are limited on the role of the physical examination and on its accuracy compared with other noninvasive tests such as conventional chest radiography or ultrasonography.

The following is an overview of the value of the clinical history and physical examination in detecting pleural effusion and a brief review of the available information regarding its accuracy compared with other diagnostic methods.

POTENTIAL CAUSES ARE MANY

The pleurae consist of two membranes that protect the lungs, allow them to move, contribute to their shape, and prevent the alveoli at the pleural surface from becoming overdistended. Between the visceral pleura (covering the lung) and the parietal pleura (covering the diaphragm and the chest wall) is the pleural space.

In healthy adults, the pleural space contains an estimated 5 to 10 mL of pleural fluid (0.1 mg/kg body weight).¹ Pleural effusion is an accumulation of an abnormal amount of fluid in the pleural space.

Although the potential causes are many, the most common are congestive heart failure, pneumonia (40% of patients hospitalized with pneumonia have pleural effusion),^2,3 cancer, and pulmonary embolism.⁴

Because many diseases affecting different organs can cause a pleural effusion, we cannot overemphasize the importance of a thorough history and physical examination to uncover clues that will help identify its cause and narrow the diagnostic workup. For example, significant weight loss and cachexia could be due to cancer, and joint, skin, or eye symptoms could be due to a connective tissue disorder.

A thorough review of the patient’s medications is mandatory, since several medications (eg, amiodarone [Cordarone], methotrexate [Rheumatrex, Trexall], and nitrofurantoin [Macrobid]) can be associated with exudative effusions. In addition, the patient’s occupational history must be ascertained, since exposure to asbestos can raise the suspicion of a malignant disease of the pleura such as mesothelioma.

SYMPTOMS ARE NEITHER SENSITIVE NOR SPECIFIC

The symptoms of pleural effusion are neither sensitive nor specific, and many patients have manifestations of the underlying process but not of the effusion itself. The most common symptoms directly related to effusion are cough, dyspnea, and pleuritic chest pain.⁵

Cough. Many patients with a pleural effusion have a dry, nonproductive cough, a consequence of inflammation of the pleurae or compression of the bronchial walls. Although this symptom is rarely helpful in diagnosing a pleural effusion, if accompanied by purulent sputum it suggests pneumonia, and if complicated by hemoptysis it suggests cancer or pulmonary embolism.

Dyspnea is a consequence of a combination of a restrictive lung defect, a ventilation-perfusion mismatch, and a decrease in cardiac output. Although large pleural effusions reduce lung volume and are generally associated with dyspnea, the symptoms may be out of proportion to the size of the effusion, and patients with small to moderate effusions may also have shortness of breath if their baseline lung function is poor.²

Chest pain accompanying a pleural effusion suggests inflammation of the parietal pleura,⁶ but could be due to cancer in the chest wall and ribs—or to a benign disease of the thoracic wall such as rib fracture or costo-chondritis.

Pain of pleural origin can remain localized to the adjacent area of the chest, but sometimes it is referred to other areas. If the diaphragmatic pleura is involved, the pain is in many cases referred to the ipsilateral shoulder.⁵ Pain may also be referred to the abdomen.

Pleuritic chest pain is described as being worse with deep inspiration or when lying down. It is common in patients with pulmonary embolism, parapneumonic effusion, or viral pleurisy, but it can also occur in patients with pneumothorax or pericarditis. A dull, aching chest pain may be due to an underlying pleural malignancy.⁷

PHYSICAL EXAMINATION: LONG TRADITION, FEW DATA

Our knowledge of the role of physical examination in detecting pleural effusion is still based mostly on expert opinion and on small case series.^8,9

Table 1 lists the most common physical signs of pleural effusion^10–15; Table 2 lists some less common (anecdotal) signs.^11,14–16 The sensitivities and specificities of the different signs in detecting pleural effusion have not been extensively studied. The limited data suggest that clinical acumen is less accurate than ultrasonography of the chest, but certain reports found it about as accurate as standard chest radiography.

Diacon et al¹⁷ assessed the accuracy of clinical examination and ultrasonography for selecting pleural puncture sites in 67 patients. Compared with ultrasonography as the gold standard, clinical examination had a sensitivity of 76%, a specificity of 60%, a positive predictive value of 85%, and a negative predictive value of 45%.

Patterson et al¹¹ prospectively compared physical examination (including auscultation, percussion, and tactile fremitus) with bedside ultrasonography and found that physical examination had a lower sensitivity (53% vs 80%, respectively) but a similar specificity (71%).

 

 

Bigger effusions are easier to detect

The physical findings are related to the volume of fluid in the pleural effusion and its effects on the chest wall, diaphragm, and lungs. Physical findings are generally normal if less than 300 mL of fluid is present, whereas large effusions (> 1,500 mL) can be associated with significant asymmetry of chest expansion and bulging of intercostal spaces.

Table 3 shows some of the common physical findings, depending on the amount of pleural fluid present.

Inspection

Although inspection of the chest is not very helpful in detecting a pleural effusion, it can provide other relevant information such as the respiratory rate and the breathing position adopted by the patient (patients with a large pleural effusion may have orthopnea); it can also reveal abnormalities in the shape of the thorax such as the increased anteroposterior diameter (“barrel shape”) seen in patients with chronic obstructive pulmonary disease.¹⁸

In addition, by inspection we can assess the expansion of the thorax. The utility of inspecting chest expansion to detect lung restriction was first noted by Laennec¹⁹ in 1821. A simple method of evaluating chest expansion is to place a measuring tape around the chest at the level of the nipples to compare the circumference at end-inspiration and at end-expiration.²⁰ In the absence of emphysema, the difference should be at least 2 inches. An expansion of 1.5 inches or less is considered abnormal.²¹ More relevant to pleural effusion than the amount of overall chest expansion is whether the expansion is symmetrical, which we can assess by palpation.

Palpation

Signs of pleural effusion that can be detected by palpation include asymmetric chest expansion and asymmetric tactile fremitus.

Chest expansion can be evaluated by placing your hands on the patient’s back with your thumbs pointed towards the spine and asking the patient to breathe (Figure 1). In a recent study by Kalantri et al¹⁰ in 278 patients (of whom 57% had pleural effusions), asymmetric chest expansion had a sensitivity of 74% and a specificity of 91%. Furthermore, when the pretest probability of disease based on other clinical findings was applied, symmetrical chest expansion was associated with a very low probability (8%) of pleural effusion.

Tactile fremitus is defined as the vibration felt by the clinician’s hand resting on the chest wall of a patient (Figure 2).²² To elicit the sign, the clinician asks the patient to say specific words repeatedly (eg, “ninety-nine”). Asymmetry of tactile fremitus can be due to air, fluid, or tumors, and thus this sign is not specific for pleural effusion. Little information is available about its accuracy, although in the study by Kalantri et al,¹⁰ its sensitivity was 82%, its specificity was 86%, and its positive predictive value was low at 59%.

Other signs. Palpation of the chest can also help in detecting underlying disease of the thorax sometimes associated with pleurisy or pleural effusions. Chest wall tumors or skin abscesses may be related to underlying empyema, localized tenderness may be associated with rib fractures or costochondritis, and crepitus may be due to subcutaneous emphysema.

 

 

Percussion

The chest can be percussed directly with the tips of the fingers of one hand or indirectly by placing a third finger against the surface to be percussed. There are two main techniques used to detect pleural effusions: comparative percussion and auscultatory percussion.

The comparative percussion technique involves comparing the sounds (dullness or hyperresonance) on the right vs the left hemithorax. Dullness may indicate pleural effusion (Figure 3). This is the technique introduced in the 18th century by Auenbrugger and Forbes,²³ who proposed that dullness is always present in a pleural effusion, although it may be difficult to detect if the effusion is bilateral.²⁴

Since other conditions such as consolidation of the lung and atelectasis can also be associated with dullness to percussion, some authors advocate percussion in the lateral supine position to detect a shift in the dullness that would indicate movement of fluid in the chest.²⁵

The sensitivity of comparative chest percussion and its accuracy related to the size of the effusion are unknown. Kalantri et al¹⁰ found that dullness to percussion had a positive predictive value of only 55% but a negative predictive value of 97%, suggesting that the absence of the sign is very helpful in ruling out an effusion.

According to classic textbook descriptions,²⁶ percussive sounds penetrate a maximum of 6 cm (2 cm of body wall thickness and 4 cm of lung), and at least 500 mL of fluid must be present in order to be able to detect an effusion by physical examination.^2,8 Most of these descriptions are based on original studies done in cadavers more than 100 years ago.

The auscultatory percussion technique was first described by Laennec and used to delineate the size of several organs by placing the stethoscope directly above the structure to be outlined, followed by percussion from the periphery towards the organ of interest. The original technique was subsequently modified for the examination of the chest by Guarino.²⁷

This method consists of tapping lightly the manubrium sterni with the distal phalanx of the index or middle finger while listening over the posterior chest wall with a stethoscope (Figure 4). The patient must be in the sitting or standing position with the arms resting at the sides or on the thighs. Percussion is applied with equal intensity over the manubrium sterni while the physician auscultates each posterior hemithorax from top to bottom, comparing the sounds on the two sides and trying to identify dullness to percussion.

In the original description, percussion was limited to the manubrium in an attempt to avoid other solid structures (such as the left ventricle) that would interfere with the transmission of the sounds.²⁷ The authors modified this technique for the detection of pleural effusion (Figure 5): with the patient sitting up and his or her back facing the examiner, a stethoscope is placed approximately 3 cm below the last rib in the mid-scapular line. The physician then proceeds to percuss with his or her free hand (by finger flicking or the pulp of a finger) along three or more parallel lines from the apex of each hemithorax perpendicularly downward toward the base to identify dullness to percussion.¹²

Although auscultatory percussion was used initially to try to detect lung lesions, masses and consolidations, Guarino and Guarino¹² found this technique to be highly effective in detecting pleural effusion. In a prospective blinded study in 118 patients, this method was highly (95%) sensitive and 100% specific in detecting pleural effusion, even in patients with obesity, pneumonia, or other pleural abnormalities. Of note, their findings suggested that auscultatory percussion can detect as little as 50 mL of pleural fluid.

Bohadana et al¹³ compared auscultatory and conventional percussion with chest radiographic findings in 281 patients. They found that auscultatory percussion was 100% sensitive for detecting large pleural effusions.

However, when Bourke et al¹⁴ compared conventional and auscultatory percussion in 21 patients with abnormal radiographs, both methods had low sensitivity (15.4% vs 19.2%) but high specificity (97.3% vs 85.1%, respectively). It is important to mention that in this series only a few patients had a pleural effusion.

McDermott et al¹⁶ compared conventional and auscultatory percussion in detecting pleural effusion in 14 hospitalized patients, using ultrasonography instead of chest radiography as the gold standard for comparison. The findings on auscultatory percussion correlated better with the findings on ultrasonography than did those on conventional percussion. The authors gave no information about sensitivity or specificity.

Kalantri et al¹⁰ found that auscultatory percussion had a sensitivity of 58% and a specificity of 85%.

Auscultation

Originally described by Laennec (who invented the stethoscope),¹⁹ auscultation is perhaps the physical examination technique most used to detect pleural effusion.

Lichtenstein et al¹⁵ performed a study of auscultation in critically ill patients and found it to have a very low sensitivity (42%) but a higher specificity (90%), with an overall diagnostic accuracy of 60%. Of note, compared with chest radiography, auscultatory findings had similar sensitivity but higher accuracy.

Absent or diminished breath sounds strongly suggest an effusion.¹⁹

Egophonism. Laennec also described egophonism as a pathognomonic sign associated with a moderate degree of effusion. The word egophony comes from the Greek “ego,” which means goat; it is used to describe the change in the pronounced sound of E to A. The mechanism responsible for finding this sign in massive pleural effusions is probably upward displacement and compression or consolidation of the lung at the top of the effusion.

However, if the effusion is small, the consolidation will not be large enough to produce this sign. Similarly, other lung conditions associated with large consolidations may produce egophonism without a pleural effusion. Little is known about the predictive value of this sign, and significant interob-server variability needs to be taken into account.²⁸

Pleural rub. Pleural effusions that result from any disease that causes direct inflammation of the pleurae can be associated with a pleural rub. This sound, classically described as rubbing of unoiled leather, is pathognomonic of pleural disease but not of pleural effusion. In fact, a pleural rub will disappear once an effusion develops. Little is known about the accuracy of this finding; in the study by Kalantri et al it had a very low sensitivity (5%) but a very high specificity (99%).¹⁰ The differential diagnosis includes pleuritis, pneumonia, mesothelioma, and tumors that metastasize to the pleura.

In detecting and evaluating pleural effusion, technology has not replaced clinical skills. Yet, despite centuries of lore, data are limited on the role of the physical examination and on its accuracy compared with other noninvasive tests such as conventional chest radiography or ultrasonography.

The following is an overview of the value of the clinical history and physical examination in detecting pleural effusion and a brief review of the available information regarding its accuracy compared with other diagnostic methods.

POTENTIAL CAUSES ARE MANY

The pleurae consist of two membranes that protect the lungs, allow them to move, contribute to their shape, and prevent the alveoli at the pleural surface from becoming overdistended. Between the visceral pleura (covering the lung) and the parietal pleura (covering the diaphragm and the chest wall) is the pleural space.

In healthy adults, the pleural space contains an estimated 5 to 10 mL of pleural fluid (0.1 mg/kg body weight).¹ Pleural effusion is an accumulation of an abnormal amount of fluid in the pleural space.

Although the potential causes are many, the most common are congestive heart failure, pneumonia (40% of patients hospitalized with pneumonia have pleural effusion),^2,3 cancer, and pulmonary embolism.⁴

Because many diseases affecting different organs can cause a pleural effusion, we cannot overemphasize the importance of a thorough history and physical examination to uncover clues that will help identify its cause and narrow the diagnostic workup. For example, significant weight loss and cachexia could be due to cancer, and joint, skin, or eye symptoms could be due to a connective tissue disorder.

A thorough review of the patient’s medications is mandatory, since several medications (eg, amiodarone [Cordarone], methotrexate [Rheumatrex, Trexall], and nitrofurantoin [Macrobid]) can be associated with exudative effusions. In addition, the patient’s occupational history must be ascertained, since exposure to asbestos can raise the suspicion of a malignant disease of the pleura such as mesothelioma.

SYMPTOMS ARE NEITHER SENSITIVE NOR SPECIFIC

The symptoms of pleural effusion are neither sensitive nor specific, and many patients have manifestations of the underlying process but not of the effusion itself. The most common symptoms directly related to effusion are cough, dyspnea, and pleuritic chest pain.⁵

Cough. Many patients with a pleural effusion have a dry, nonproductive cough, a consequence of inflammation of the pleurae or compression of the bronchial walls. Although this symptom is rarely helpful in diagnosing a pleural effusion, if accompanied by purulent sputum it suggests pneumonia, and if complicated by hemoptysis it suggests cancer or pulmonary embolism.

Dyspnea is a consequence of a combination of a restrictive lung defect, a ventilation-perfusion mismatch, and a decrease in cardiac output. Although large pleural effusions reduce lung volume and are generally associated with dyspnea, the symptoms may be out of proportion to the size of the effusion, and patients with small to moderate effusions may also have shortness of breath if their baseline lung function is poor.²

Chest pain accompanying a pleural effusion suggests inflammation of the parietal pleura,⁶ but could be due to cancer in the chest wall and ribs—or to a benign disease of the thoracic wall such as rib fracture or costo-chondritis.

Pain of pleural origin can remain localized to the adjacent area of the chest, but sometimes it is referred to other areas. If the diaphragmatic pleura is involved, the pain is in many cases referred to the ipsilateral shoulder.⁵ Pain may also be referred to the abdomen.

Pleuritic chest pain is described as being worse with deep inspiration or when lying down. It is common in patients with pulmonary embolism, parapneumonic effusion, or viral pleurisy, but it can also occur in patients with pneumothorax or pericarditis. A dull, aching chest pain may be due to an underlying pleural malignancy.⁷

PHYSICAL EXAMINATION: LONG TRADITION, FEW DATA

Our knowledge of the role of physical examination in detecting pleural effusion is still based mostly on expert opinion and on small case series.^8,9

Table 1 lists the most common physical signs of pleural effusion^10–15; Table 2 lists some less common (anecdotal) signs.^11,14–16 The sensitivities and specificities of the different signs in detecting pleural effusion have not been extensively studied. The limited data suggest that clinical acumen is less accurate than ultrasonography of the chest, but certain reports found it about as accurate as standard chest radiography.

Diacon et al¹⁷ assessed the accuracy of clinical examination and ultrasonography for selecting pleural puncture sites in 67 patients. Compared with ultrasonography as the gold standard, clinical examination had a sensitivity of 76%, a specificity of 60%, a positive predictive value of 85%, and a negative predictive value of 45%.

Patterson et al¹¹ prospectively compared physical examination (including auscultation, percussion, and tactile fremitus) with bedside ultrasonography and found that physical examination had a lower sensitivity (53% vs 80%, respectively) but a similar specificity (71%).

 

 

Bigger effusions are easier to detect

The physical findings are related to the volume of fluid in the pleural effusion and its effects on the chest wall, diaphragm, and lungs. Physical findings are generally normal if less than 300 mL of fluid is present, whereas large effusions (> 1,500 mL) can be associated with significant asymmetry of chest expansion and bulging of intercostal spaces.

Table 3 shows some of the common physical findings, depending on the amount of pleural fluid present.

Inspection

Although inspection of the chest is not very helpful in detecting a pleural effusion, it can provide other relevant information such as the respiratory rate and the breathing position adopted by the patient (patients with a large pleural effusion may have orthopnea); it can also reveal abnormalities in the shape of the thorax such as the increased anteroposterior diameter (“barrel shape”) seen in patients with chronic obstructive pulmonary disease.¹⁸

In addition, by inspection we can assess the expansion of the thorax. The utility of inspecting chest expansion to detect lung restriction was first noted by Laennec¹⁹ in 1821. A simple method of evaluating chest expansion is to place a measuring tape around the chest at the level of the nipples to compare the circumference at end-inspiration and at end-expiration.²⁰ In the absence of emphysema, the difference should be at least 2 inches. An expansion of 1.5 inches or less is considered abnormal.²¹ More relevant to pleural effusion than the amount of overall chest expansion is whether the expansion is symmetrical, which we can assess by palpation.

Palpation

Signs of pleural effusion that can be detected by palpation include asymmetric chest expansion and asymmetric tactile fremitus.

Chest expansion can be evaluated by placing your hands on the patient’s back with your thumbs pointed towards the spine and asking the patient to breathe (Figure 1). In a recent study by Kalantri et al¹⁰ in 278 patients (of whom 57% had pleural effusions), asymmetric chest expansion had a sensitivity of 74% and a specificity of 91%. Furthermore, when the pretest probability of disease based on other clinical findings was applied, symmetrical chest expansion was associated with a very low probability (8%) of pleural effusion.

Tactile fremitus is defined as the vibration felt by the clinician’s hand resting on the chest wall of a patient (Figure 2).²² To elicit the sign, the clinician asks the patient to say specific words repeatedly (eg, “ninety-nine”). Asymmetry of tactile fremitus can be due to air, fluid, or tumors, and thus this sign is not specific for pleural effusion. Little information is available about its accuracy, although in the study by Kalantri et al,¹⁰ its sensitivity was 82%, its specificity was 86%, and its positive predictive value was low at 59%.

Other signs. Palpation of the chest can also help in detecting underlying disease of the thorax sometimes associated with pleurisy or pleural effusions. Chest wall tumors or skin abscesses may be related to underlying empyema, localized tenderness may be associated with rib fractures or costochondritis, and crepitus may be due to subcutaneous emphysema.

 

 

Percussion

The chest can be percussed directly with the tips of the fingers of one hand or indirectly by placing a third finger against the surface to be percussed. There are two main techniques used to detect pleural effusions: comparative percussion and auscultatory percussion.

The comparative percussion technique involves comparing the sounds (dullness or hyperresonance) on the right vs the left hemithorax. Dullness may indicate pleural effusion (Figure 3). This is the technique introduced in the 18th century by Auenbrugger and Forbes,²³ who proposed that dullness is always present in a pleural effusion, although it may be difficult to detect if the effusion is bilateral.²⁴

Since other conditions such as consolidation of the lung and atelectasis can also be associated with dullness to percussion, some authors advocate percussion in the lateral supine position to detect a shift in the dullness that would indicate movement of fluid in the chest.²⁵

The sensitivity of comparative chest percussion and its accuracy related to the size of the effusion are unknown. Kalantri et al¹⁰ found that dullness to percussion had a positive predictive value of only 55% but a negative predictive value of 97%, suggesting that the absence of the sign is very helpful in ruling out an effusion.

According to classic textbook descriptions,²⁶ percussive sounds penetrate a maximum of 6 cm (2 cm of body wall thickness and 4 cm of lung), and at least 500 mL of fluid must be present in order to be able to detect an effusion by physical examination.^2,8 Most of these descriptions are based on original studies done in cadavers more than 100 years ago.

The auscultatory percussion technique was first described by Laennec and used to delineate the size of several organs by placing the stethoscope directly above the structure to be outlined, followed by percussion from the periphery towards the organ of interest. The original technique was subsequently modified for the examination of the chest by Guarino.²⁷

This method consists of tapping lightly the manubrium sterni with the distal phalanx of the index or middle finger while listening over the posterior chest wall with a stethoscope (Figure 4). The patient must be in the sitting or standing position with the arms resting at the sides or on the thighs. Percussion is applied with equal intensity over the manubrium sterni while the physician auscultates each posterior hemithorax from top to bottom, comparing the sounds on the two sides and trying to identify dullness to percussion.

In the original description, percussion was limited to the manubrium in an attempt to avoid other solid structures (such as the left ventricle) that would interfere with the transmission of the sounds.²⁷ The authors modified this technique for the detection of pleural effusion (Figure 5): with the patient sitting up and his or her back facing the examiner, a stethoscope is placed approximately 3 cm below the last rib in the mid-scapular line. The physician then proceeds to percuss with his or her free hand (by finger flicking or the pulp of a finger) along three or more parallel lines from the apex of each hemithorax perpendicularly downward toward the base to identify dullness to percussion.¹²

Although auscultatory percussion was used initially to try to detect lung lesions, masses and consolidations, Guarino and Guarino¹² found this technique to be highly effective in detecting pleural effusion. In a prospective blinded study in 118 patients, this method was highly (95%) sensitive and 100% specific in detecting pleural effusion, even in patients with obesity, pneumonia, or other pleural abnormalities. Of note, their findings suggested that auscultatory percussion can detect as little as 50 mL of pleural fluid.

Bohadana et al¹³ compared auscultatory and conventional percussion with chest radiographic findings in 281 patients. They found that auscultatory percussion was 100% sensitive for detecting large pleural effusions.

However, when Bourke et al¹⁴ compared conventional and auscultatory percussion in 21 patients with abnormal radiographs, both methods had low sensitivity (15.4% vs 19.2%) but high specificity (97.3% vs 85.1%, respectively). It is important to mention that in this series only a few patients had a pleural effusion.

McDermott et al¹⁶ compared conventional and auscultatory percussion in detecting pleural effusion in 14 hospitalized patients, using ultrasonography instead of chest radiography as the gold standard for comparison. The findings on auscultatory percussion correlated better with the findings on ultrasonography than did those on conventional percussion. The authors gave no information about sensitivity or specificity.

Kalantri et al¹⁰ found that auscultatory percussion had a sensitivity of 58% and a specificity of 85%.

Auscultation

Originally described by Laennec (who invented the stethoscope),¹⁹ auscultation is perhaps the physical examination technique most used to detect pleural effusion.

Lichtenstein et al¹⁵ performed a study of auscultation in critically ill patients and found it to have a very low sensitivity (42%) but a higher specificity (90%), with an overall diagnostic accuracy of 60%. Of note, compared with chest radiography, auscultatory findings had similar sensitivity but higher accuracy.

Absent or diminished breath sounds strongly suggest an effusion.¹⁹

Egophonism. Laennec also described egophonism as a pathognomonic sign associated with a moderate degree of effusion. The word egophony comes from the Greek “ego,” which means goat; it is used to describe the change in the pronounced sound of E to A. The mechanism responsible for finding this sign in massive pleural effusions is probably upward displacement and compression or consolidation of the lung at the top of the effusion.

However, if the effusion is small, the consolidation will not be large enough to produce this sign. Similarly, other lung conditions associated with large consolidations may produce egophonism without a pleural effusion. Little is known about the predictive value of this sign, and significant interob-server variability needs to be taken into account.²⁸

Pleural rub. Pleural effusions that result from any disease that causes direct inflammation of the pleurae can be associated with a pleural rub. This sound, classically described as rubbing of unoiled leather, is pathognomonic of pleural disease but not of pleural effusion. In fact, a pleural rub will disappear once an effusion develops. Little is known about the accuracy of this finding; in the study by Kalantri et al it had a very low sensitivity (5%) but a very high specificity (99%).¹⁰ The differential diagnosis includes pleuritis, pneumonia, mesothelioma, and tumors that metastasize to the pleura.

In detecting and evaluating pleural effusion, technology has not replaced clinical skills. Yet, despite centuries of lore, data are limited on the role of the physical examination and on its accuracy compared with other noninvasive tests such as conventional chest radiography or ultrasonography.

The following is an overview of the value of the clinical history and physical examination in detecting pleural effusion and a brief review of the available information regarding its accuracy compared with other diagnostic methods.

POTENTIAL CAUSES ARE MANY

The pleurae consist of two membranes that protect the lungs, allow them to move, contribute to their shape, and prevent the alveoli at the pleural surface from becoming overdistended. Between the visceral pleura (covering the lung) and the parietal pleura (covering the diaphragm and the chest wall) is the pleural space.

In healthy adults, the pleural space contains an estimated 5 to 10 mL of pleural fluid (0.1 mg/kg body weight).¹ Pleural effusion is an accumulation of an abnormal amount of fluid in the pleural space.

Although the potential causes are many, the most common are congestive heart failure, pneumonia (40% of patients hospitalized with pneumonia have pleural effusion),^2,3 cancer, and pulmonary embolism.⁴

Because many diseases affecting different organs can cause a pleural effusion, we cannot overemphasize the importance of a thorough history and physical examination to uncover clues that will help identify its cause and narrow the diagnostic workup. For example, significant weight loss and cachexia could be due to cancer, and joint, skin, or eye symptoms could be due to a connective tissue disorder.

A thorough review of the patient’s medications is mandatory, since several medications (eg, amiodarone [Cordarone], methotrexate [Rheumatrex, Trexall], and nitrofurantoin [Macrobid]) can be associated with exudative effusions. In addition, the patient’s occupational history must be ascertained, since exposure to asbestos can raise the suspicion of a malignant disease of the pleura such as mesothelioma.

SYMPTOMS ARE NEITHER SENSITIVE NOR SPECIFIC

The symptoms of pleural effusion are neither sensitive nor specific, and many patients have manifestations of the underlying process but not of the effusion itself. The most common symptoms directly related to effusion are cough, dyspnea, and pleuritic chest pain.⁵

Cough. Many patients with a pleural effusion have a dry, nonproductive cough, a consequence of inflammation of the pleurae or compression of the bronchial walls. Although this symptom is rarely helpful in diagnosing a pleural effusion, if accompanied by purulent sputum it suggests pneumonia, and if complicated by hemoptysis it suggests cancer or pulmonary embolism.

Dyspnea is a consequence of a combination of a restrictive lung defect, a ventilation-perfusion mismatch, and a decrease in cardiac output. Although large pleural effusions reduce lung volume and are generally associated with dyspnea, the symptoms may be out of proportion to the size of the effusion, and patients with small to moderate effusions may also have shortness of breath if their baseline lung function is poor.²

Chest pain accompanying a pleural effusion suggests inflammation of the parietal pleura,⁶ but could be due to cancer in the chest wall and ribs—or to a benign disease of the thoracic wall such as rib fracture or costo-chondritis.

Pain of pleural origin can remain localized to the adjacent area of the chest, but sometimes it is referred to other areas. If the diaphragmatic pleura is involved, the pain is in many cases referred to the ipsilateral shoulder.⁵ Pain may also be referred to the abdomen.

Pleuritic chest pain is described as being worse with deep inspiration or when lying down. It is common in patients with pulmonary embolism, parapneumonic effusion, or viral pleurisy, but it can also occur in patients with pneumothorax or pericarditis. A dull, aching chest pain may be due to an underlying pleural malignancy.⁷

PHYSICAL EXAMINATION: LONG TRADITION, FEW DATA

Our knowledge of the role of physical examination in detecting pleural effusion is still based mostly on expert opinion and on small case series.^8,9

Table 1 lists the most common physical signs of pleural effusion^10–15; Table 2 lists some less common (anecdotal) signs.^11,14–16 The sensitivities and specificities of the different signs in detecting pleural effusion have not been extensively studied. The limited data suggest that clinical acumen is less accurate than ultrasonography of the chest, but certain reports found it about as accurate as standard chest radiography.

Diacon et al¹⁷ assessed the accuracy of clinical examination and ultrasonography for selecting pleural puncture sites in 67 patients. Compared with ultrasonography as the gold standard, clinical examination had a sensitivity of 76%, a specificity of 60%, a positive predictive value of 85%, and a negative predictive value of 45%.

Patterson et al¹¹ prospectively compared physical examination (including auscultation, percussion, and tactile fremitus) with bedside ultrasonography and found that physical examination had a lower sensitivity (53% vs 80%, respectively) but a similar specificity (71%).

 

 

Bigger effusions are easier to detect

The physical findings are related to the volume of fluid in the pleural effusion and its effects on the chest wall, diaphragm, and lungs. Physical findings are generally normal if less than 300 mL of fluid is present, whereas large effusions (> 1,500 mL) can be associated with significant asymmetry of chest expansion and bulging of intercostal spaces.

Table 3 shows some of the common physical findings, depending on the amount of pleural fluid present.

Inspection

Although inspection of the chest is not very helpful in detecting a pleural effusion, it can provide other relevant information such as the respiratory rate and the breathing position adopted by the patient (patients with a large pleural effusion may have orthopnea); it can also reveal abnormalities in the shape of the thorax such as the increased anteroposterior diameter (“barrel shape”) seen in patients with chronic obstructive pulmonary disease.¹⁸

In addition, by inspection we can assess the expansion of the thorax. The utility of inspecting chest expansion to detect lung restriction was first noted by Laennec¹⁹ in 1821. A simple method of evaluating chest expansion is to place a measuring tape around the chest at the level of the nipples to compare the circumference at end-inspiration and at end-expiration.²⁰ In the absence of emphysema, the difference should be at least 2 inches. An expansion of 1.5 inches or less is considered abnormal.²¹ More relevant to pleural effusion than the amount of overall chest expansion is whether the expansion is symmetrical, which we can assess by palpation.

Palpation

Signs of pleural effusion that can be detected by palpation include asymmetric chest expansion and asymmetric tactile fremitus.

Chest expansion can be evaluated by placing your hands on the patient’s back with your thumbs pointed towards the spine and asking the patient to breathe (Figure 1). In a recent study by Kalantri et al¹⁰ in 278 patients (of whom 57% had pleural effusions), asymmetric chest expansion had a sensitivity of 74% and a specificity of 91%. Furthermore, when the pretest probability of disease based on other clinical findings was applied, symmetrical chest expansion was associated with a very low probability (8%) of pleural effusion.

Tactile fremitus is defined as the vibration felt by the clinician’s hand resting on the chest wall of a patient (Figure 2).²² To elicit the sign, the clinician asks the patient to say specific words repeatedly (eg, “ninety-nine”). Asymmetry of tactile fremitus can be due to air, fluid, or tumors, and thus this sign is not specific for pleural effusion. Little information is available about its accuracy, although in the study by Kalantri et al,¹⁰ its sensitivity was 82%, its specificity was 86%, and its positive predictive value was low at 59%.

Other signs. Palpation of the chest can also help in detecting underlying disease of the thorax sometimes associated with pleurisy or pleural effusions. Chest wall tumors or skin abscesses may be related to underlying empyema, localized tenderness may be associated with rib fractures or costochondritis, and crepitus may be due to subcutaneous emphysema.

 

 

Percussion

The chest can be percussed directly with the tips of the fingers of one hand or indirectly by placing a third finger against the surface to be percussed. There are two main techniques used to detect pleural effusions: comparative percussion and auscultatory percussion.

The comparative percussion technique involves comparing the sounds (dullness or hyperresonance) on the right vs the left hemithorax. Dullness may indicate pleural effusion (Figure 3). This is the technique introduced in the 18th century by Auenbrugger and Forbes,²³ who proposed that dullness is always present in a pleural effusion, although it may be difficult to detect if the effusion is bilateral.²⁴

Since other conditions such as consolidation of the lung and atelectasis can also be associated with dullness to percussion, some authors advocate percussion in the lateral supine position to detect a shift in the dullness that would indicate movement of fluid in the chest.²⁵

The sensitivity of comparative chest percussion and its accuracy related to the size of the effusion are unknown. Kalantri et al¹⁰ found that dullness to percussion had a positive predictive value of only 55% but a negative predictive value of 97%, suggesting that the absence of the sign is very helpful in ruling out an effusion.

According to classic textbook descriptions,²⁶ percussive sounds penetrate a maximum of 6 cm (2 cm of body wall thickness and 4 cm of lung), and at least 500 mL of fluid must be present in order to be able to detect an effusion by physical examination.^2,8 Most of these descriptions are based on original studies done in cadavers more than 100 years ago.

The auscultatory percussion technique was first described by Laennec and used to delineate the size of several organs by placing the stethoscope directly above the structure to be outlined, followed by percussion from the periphery towards the organ of interest. The original technique was subsequently modified for the examination of the chest by Guarino.²⁷

This method consists of tapping lightly the manubrium sterni with the distal phalanx of the index or middle finger while listening over the posterior chest wall with a stethoscope (Figure 4). The patient must be in the sitting or standing position with the arms resting at the sides or on the thighs. Percussion is applied with equal intensity over the manubrium sterni while the physician auscultates each posterior hemithorax from top to bottom, comparing the sounds on the two sides and trying to identify dullness to percussion.

In the original description, percussion was limited to the manubrium in an attempt to avoid other solid structures (such as the left ventricle) that would interfere with the transmission of the sounds.²⁷ The authors modified this technique for the detection of pleural effusion (Figure 5): with the patient sitting up and his or her back facing the examiner, a stethoscope is placed approximately 3 cm below the last rib in the mid-scapular line. The physician then proceeds to percuss with his or her free hand (by finger flicking or the pulp of a finger) along three or more parallel lines from the apex of each hemithorax perpendicularly downward toward the base to identify dullness to percussion.¹²

Although auscultatory percussion was used initially to try to detect lung lesions, masses and consolidations, Guarino and Guarino¹² found this technique to be highly effective in detecting pleural effusion. In a prospective blinded study in 118 patients, this method was highly (95%) sensitive and 100% specific in detecting pleural effusion, even in patients with obesity, pneumonia, or other pleural abnormalities. Of note, their findings suggested that auscultatory percussion can detect as little as 50 mL of pleural fluid.

Bohadana et al¹³ compared auscultatory and conventional percussion with chest radiographic findings in 281 patients. They found that auscultatory percussion was 100% sensitive for detecting large pleural effusions.

However, when Bourke et al¹⁴ compared conventional and auscultatory percussion in 21 patients with abnormal radiographs, both methods had low sensitivity (15.4% vs 19.2%) but high specificity (97.3% vs 85.1%, respectively). It is important to mention that in this series only a few patients had a pleural effusion.

McDermott et al¹⁶ compared conventional and auscultatory percussion in detecting pleural effusion in 14 hospitalized patients, using ultrasonography instead of chest radiography as the gold standard for comparison. The findings on auscultatory percussion correlated better with the findings on ultrasonography than did those on conventional percussion. The authors gave no information about sensitivity or specificity.

Kalantri et al¹⁰ found that auscultatory percussion had a sensitivity of 58% and a specificity of 85%.

Auscultation

Originally described by Laennec (who invented the stethoscope),¹⁹ auscultation is perhaps the physical examination technique most used to detect pleural effusion.

Lichtenstein et al¹⁵ performed a study of auscultation in critically ill patients and found it to have a very low sensitivity (42%) but a higher specificity (90%), with an overall diagnostic accuracy of 60%. Of note, compared with chest radiography, auscultatory findings had similar sensitivity but higher accuracy.

Absent or diminished breath sounds strongly suggest an effusion.¹⁹

Egophonism. Laennec also described egophonism as a pathognomonic sign associated with a moderate degree of effusion. The word egophony comes from the Greek “ego,” which means goat; it is used to describe the change in the pronounced sound of E to A. The mechanism responsible for finding this sign in massive pleural effusions is probably upward displacement and compression or consolidation of the lung at the top of the effusion.

However, if the effusion is small, the consolidation will not be large enough to produce this sign. Similarly, other lung conditions associated with large consolidations may produce egophonism without a pleural effusion. Little is known about the predictive value of this sign, and significant interob-server variability needs to be taken into account.²⁸

Pleural rub. Pleural effusions that result from any disease that causes direct inflammation of the pleurae can be associated with a pleural rub. This sound, classically described as rubbing of unoiled leather, is pathognomonic of pleural disease but not of pleural effusion. In fact, a pleural rub will disappear once an effusion develops. Little is known about the accuracy of this finding; in the study by Kalantri et al it had a very low sensitivity (5%) but a very high specificity (99%).¹⁰ The differential diagnosis includes pleuritis, pneumonia, mesothelioma, and tumors that metastasize to the pleura.