PULMONOLOGY, COUGH

Cough Cough is an important physiologic mechanism that defends against respiratory pathogens and helps clear the tracheobronchial tree of mucus, foreign particles, and noxious aerosols. Excessive cough is one of the most common symptoms for which patients seek medical care and may represent up to one-third of a pulmonologist's outpatient practice referrals. Persistent severe cough, seen in interstitial lung disease or bronchiectasis, may impair respiration as well as disrupt sleep and social functioning. Bronchospasm (brought on by repetitive forced exhalation), syncope, rib fractures, and urinary incontinence are all potential complications. A reduced or absent cough, seen in some postoperative patients or those with neuromuscular disease, will reduce clearance of secretions and may impair oxygenation. Cough may be voluntary or involuntary. Involuntary cough is stimulated by vagal afferent receptors in the trachea, especially at the carina, and the larynx but also from others throughout the head and neck. Stimulation of cough receptors may be mechanical, as in cases of aspiration, or irritative. Clinical Findings It is important to distinguish acute (< 3 weeks) from subacute (3–8 weeks) and chronic (> 8 weeks) cough. Acute cough most commonly follows viral or bacterial upper respiratory tract infection. Within 2 days after onset of the common cold, 85% of untreated patients cough; 25% are still coughing 14 days later; in a few, cough will persist for 6–8 weeks. Many patients with persistent cough following upper respiratory tract infection have underlying asthma. Other causes of acute cough include aspiration, pneumonia, pulmonary embolism, and pulmonary edema. The most common cause of chronic cough is a low-grade chronic bronchitis secondary to exposure to tobacco smoke, though smokers do not commonly seek medical attention for this problem. Over 90% of nonsmokers presenting for evaluation of chronic cough suffer from postnasal drip, gastroesophageal reflux disease, or asthma (even without other symptoms). Angiotensin-converting enzyme (ACE) inhibitors have become another common cause. In primary care settings, single causes predominate. The character and timing of chronic cough and the presence or absence of sputum production do not permit an etiologic diagnosis and should not be used as the sole basis for empiric therapy. The history and physical examination should attempt to identify anatomic locations of the afferent limb of the cough reflex in light of the common causes listed above. A nasal discharge, frequent need to clear the throat, and mucoid or mucopurulent secretions in the posterior pharynx suggest an upper airway cough syndrome. Sinus imaging may be diagnostic of acute or chronic sinusitis. Wheezing on chest auscultation or airflow obstruction on pulmonary function tests suggests asthma. In cough-variant asthma, methacholine bronchoprovocation testing may be positive in the absence of clinical findings of asthma. Gastroesophageal reflux disease is an important cause of chronic cough but is associated with the fewest clinical clues; cough, even in the absence of heartburn, may be the only symptom. Barium swallow is specific but insensitive, and esophageal pH monitoring may be necessary for diagnosis. Chest imaging is best reserved for evaluation of cough in smokers; in patients with hemoptysis or constitutional symptoms, such as fever and weight loss; and in persons with chronic cough that does not respond to initial therapy. Treatment See Related Guideline from CURRENT Practice Guidelines in Primary Care 2007 The first step is to eliminate irritant exposures such as tobacco smoke (primary or secondary) and occupational agents and to discontinue medications such as ACE inhibitors or -blockers, including eyedrops. Cough due to ACE inhibitors should subside within 1–4 days after discontinuing the medication, though it may take several weeks. Upper airway cough syndrome due to allergic rhinitis that does not respond to antihistamines should be treated with intranasal corticosteroids. Chronic sinusitis may require prolonged antibiotics directed against Haemophilus influenzae. Cough caused by asthma that does not respond after 2 weeks of bronchodilators and corticosteroids suggests another contributing condition. Cough due to gastroesophageal reflux disease is difficult to treat and may require proton pump inhibitors, since H2-blockers may be inadequate. Patients whose cough began after an upper respiratory tract infection usually respond to treatment with an antihistamine-decongestant combination or treatment for asthma. Chang AB et al. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004823. [PMID: 15846735] Diagnosis and management of cough: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):1S–292S. [PMID: [PMID: 16428686 through 16428721] Hewlett EL et al. Clinical practice. Pertussis—not just for kids. N Engl J Med. 2005 Mar 24;352(12):1215–22. [PMID: 15788498] Morice AH et al; ERS Task Force. The diagnosis and management of chronic cough. Eur Respir J. 2004 Sep;24(3):481–92. [PMID: 15358710]

Physical Examination Examination of the patient with suspected pulmonary disease includes inspection, palpation, percussion, and auscultation of the chest. An efficient approach begins with observing the pattern of breathing, auscultation of the chest, and inspection for extrapulmonary signs of pulmonary disease. More detailed examination follows from initial findings. The pattern of breathing refers to the respiratory rate and rhythm, the depth of breathing or tidal volume, and the relative amount of time spent in inspiration and expiration. Normal values are a rate of 12–14 breaths per minute, tidal volumes of 5 mL/kg, and a ratio of inspiratory to expiratory time of 2:3. Tachypnea is an increased rate of breathing and is commonly associated with a decrease in tidal volume. Respiratory rhythm is normally regular, with a sigh (1.5–2 times normal tidal volume) every 90 breaths or so to prevent collapse of alveoli and atelectasis. Alterations in the rhythm of breathing include rapid, shallow breathing, seen in restrictive lung disease and as a precursor to respiratory failure; Kussmaul breathing, rapid large-volume breathing indicating intense stimulation of the respiratory center, seen in metabolic acidosis; and Cheyne-Stokes respiration, a rhythmic waxing and waning of both rate and tidal volumes that includes regular periods of apnea. This last pattern is seen in patients with end-stage left ventricular failure or neurologic disease and in many normal persons at high altitude, especially during sleep. During normal quiet breathing, the primary muscle of respiration is the diaphragm. Movement of the chest wall is minimal. The use of accessory muscles of respiration, the intercostal and sternocleidomastoid muscles, indicates high work of breathing. At rest, the use of accessory muscles is a sign of significant pulmonary impairment. As the diaphragm contracts, it pushes the abdominal contents down. Hence, the chest and abdominal wall normally expand simultaneously. Expansion of the chest but collapse of the abdomen on inspiration indicates weakness of the diaphragm. The chest normally expands symmetrically. Asymmetric expansion suggests unilateral volume loss, as in atelectasis or pleural effusion, unilateral airway obstruction, asymmetric pulmonary or pleural fibrosis, or splinting from chest pain. The examiner may palpate as follows: the trachea at the suprasternal notch, to detect shifts in the mediastinum; on the posterior chest wall, to gauge fremitus and the transmission through the lungs of vibrations of spoken words; and on the anterior chest wall to assess the cardiac impulse. All these maneuvers are characterized by low interobserver agreement. Chest percussion identifies dull areas that correspond to lung consolidation or pleural effusion or hyperresonant areas suggesting emphysema or pneumothorax. Percussion has a low sensitivity (10–20% in several studies) compared with chest radiographs to detect abnormalities. Specificity is high (85–99%). Since an insensitive test is a poor screening examination, percussion and palpation are not necessary in every patient. These techniques do serve as important confirmatory tests in specific patients when the prior probability of a finding is increased. For example, in a patient with a suspected tension pneumothorax, the finding of tracheal shift and hyperresonance can be lifesaving, permitting immediate decompression of the affected side. Auscultation of the chest depends on a reliable and consistent classification of auditory findings. Normal lung sounds heard over the periphery of the lung are called vesicular ; . They have a gentle, rustling quality heard throughout inspiration that fades during expiration. Normal sounds heard over the suprasternal notch are called tracheal or bronchial lung sounds . They are louder, higher-pitched, and have a hollow quality that tends to be louder on expiration. Bronchial lung sounds heard over the periphery of the lung are abnormal and imply consolidation. Globally diminished lung sounds are an important finding predictive of significant airflow obstruction . Audio Vesicular breath sounds recorded in a person with normal lungs. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Audio Bronchial breath sounds recorded over an area of consolidation in a person with pneumonia. Note the loud expiratory phase, which helps to clarify these sounds as bronchial. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Audio Recording of normal vesicular lung sounds. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Audio Recording of breath sounds in a person with emphysema. Note the diminished intensity of breath sounds in emphysema. The obstruction to air flow is more severe in expiration than in inspiration, and expiration is prolonged. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Abnormal lung sounds ("adventitious" breath sounds) may be continuous (> 80 ms in duration) or discontinuous (< 20 ms). Continuous lung sounds are divided into wheezes , which are high-pitched, musical, and have a distinct whistling quality; and rhonchi , which are lower-pitched, sonorous, and may have a gurgling quality. Wheezes occur in the setting of bronchospasm, mucosal edema, or excessive secretions. In each case, the airway is narrowed to the point where adjacent airway walls flutter as airflow is limited. Rhonchi originate in the larger airways when excessive secretions and abnormal airway collapsibility cause repetitive rupture of fluid films. Rhonchi frequently clear after cough. Audio Lung sound: sibilant rhonchus, often called "wheezes." (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Audio Lung sound: sonorous rhonchus. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Discontinuous lung sounds are called crackles—brief, discrete, nonmusical sounds with a popping quality. Fine crackles are soft, high-pitched, and crisp (< 10 ms in duration) . They are formed by the explosive opening of small airways previously held closed by surface forces and are heard in interstitial diseases or early pulmonary edema. Coarse crackles are louder, lower-pitched, and slightly longer in duration (< 20 ms) and probably result from gas bubbling through fluid . Coarse crackles are heard in pneumonia, obstructive lung disease, and late pulmonary edema. Audio Discontinuous lung sound: fine rales. Note that, in general, each individual rale is less loud and of shorter duration than the coarse rales. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Audio Discontinuous lung sound: coarse rales. (Reproduced, with permission, from Raymond L.H. Murphy, Jr., MD: A Simplified Introduction to Lung Sounds [audio tape], 1977.) Interobserver agreement regarding auscultatory findings is good. The clinical usefulness of these findings is also well established. The presence of wheezes on physical examination is a powerful predictor of obstructive lung disease. The absence of wheezes is not helpful since patients may have significant airflow limitation without wheezing. Such patients will have globally diminished lung sounds as the clinical clue to their obstructive lung disease. Normal lung sounds exclude significant airway obstruction. The timing and character of crackles can reliably distinguish different pulmonary disorders. Fine, late inspiratory crackles suggest pulmonary fibrosis, while early coarse crackles suggest pneumonia or heart failure. Extrapulmonary signs of intrinsic pulmonary disease include digital clubbing, cyanosis, elevation of central venous pressures, and lower extremity edema. Digital clubbing (see photograph) refers to structural changes at the base of the nails that include softening of the nail bed and loss of the normal 150-degree angle between the nail and the cuticle. The distal phalanx is convex and enlarged: its thickness is equal to or greater than the thickness of the distal interphalangeal joint. Symmetric clubbing may be a normal variant but more commonly is a sign of underlying disease. Clubbing is seen in patients with chronic infections of the lungs and pleura (lung abscess, empyema, bronchiectasis, cystic fibrosis), malignancies of the lungs and pleura, chronic interstitial lung disease (idiopathic pulmonary fibrosis), and arteriovenous malformations. It does not normally accompany asthma or COPD; when seen in the latter, concomitant lung cancer should be suspected. It is observed less often in small-cell cancer than in other histologic types. Clubbing is not specific to pulmonary disorders; it is also seen in cyanotic congenital heart disease, infective endocarditis, cirrhosis, and inflammatory bowel disease. Hypertrophic pulmonary osteoarthropathy is a syndrome of digital clubbing, chronic proliferative periostitis of the long bones, and synovitis. It is seen in the same conditions as digital clubbing but is particularly common in bronchogenic carcinoma. The cause of clubbing and hypertrophic osteoarthropathy is not known with certainty, but the disorder may reflect platelet clumping and local release of platelet-derived growth factor at the nail bed. Both clubbing and osteoarthropathy may resolve with appropriate treatment of the underlying disease. Cyanosis is a blue or bluish-gray discoloration of the skin and mucous membranes caused by increased amounts (> 5 g/dL) of unsaturated hemoglobin in capillary blood. Since the oxygen saturation at which cyanosis becomes clinically apparent is a function of hemoglobin concentration, anemia may prevent cyanosis from appearing while polycythemia may lead to cyanosis in the setting of mild hypoxemia. Cyanosis is therefore not a reliable indicator of hypoxemia but should prompt direct measurement of arterial PO2 or of hemoglobin saturation. Fig. Clubbing of the fingers. (Reproduced, with permission, from Cheitlin MD, Sokolow M, McIlroy MB: Clinical Cardiology, 6th ed. Originally published by Appleton & Lange. Copyright © 1993 by The McGraw-Hill Companies, Inc.) Estimation of central venous pressure (CVP) (see illustration) and assessment of lower extremity edema are indirect measures of pulmonary hypertension, the major cardiovascular complication of chronic lung disease. Estimation of CVP can be done with precision in many patients. Elevated CVP is a pathologic finding associated with impaired ventricular function, pericardial effusion or restriction, valvular heart disease, and chronic obstructive or restrictive lung disease. Peripheral edema is a nonspecific finding that, in the setting of chronic lung disease, suggests right ventricular failure. Bettencourt PE et al. Clinical utility of chest auscultation in common pulmonary diseases. Am J Respir Crit Care Med. 1994 Nov;150(5 Pt 1):1291–7. [PMID: 7952555] Myers KA et al. Does this patient have clubbing? JAMA. 2001 Jul 18;286(3):341–7. [PMID: 11466101]

Pulmonary Function Tests Standard pulmonary function tests measure airflow rates, lung volumes, and the ability of the lung to transfer gas across the alveolar-capillary membrane. Indications for pulmonary function testing include assessment of the type and extent of lung dysfunction; diagnosis of causes of dyspnea and cough; detection of early evidence of lung dysfunction; longitudinal surveillance in occupational settings; follow-up of response to therapy; preoperative assessment; and disability evaluation. Contraindications to pulmonary function testing include acute severe asthma, respiratory distress, angina aggravated by testing, pneumothorax, ongoing hemoptysis, and active tuberculosis. Many test results are effort-dependent, and some patients may be too impaired to make a maximal effort. Suboptimal effort limits validity and is a common cause of misinterpretation of results. All pulmonary function tests are measured against predicted values derived from large studies of healthy subjects. In general, these predictions vary with age, gender, height and, to a lesser extent, weight and ethnicity. Spirometry (see box) and measurement of lung volumes allow assessment of the presence and severity of obstructive and restrictive pulmonary dysfunction. Obstructive dysfunction is marked by a reduction in airflow rates judged by a fall in the ratio of FEV1 (forced expiratory volume in the first second) to FVC (forced vital capacity). Causes include asthma, COPD (chronic bronchitis and emphysema), bronchiectasis, bronchiolitis, and upper airway obstruction. Restrictive dysfunction is marked by a reduction in lung volumes with a normal to increased FEV1/FVC ratio. Severity is graded by the reduction in total lung capacity. A reduced FVC suggests pulmonary restriction but is not diagnostic. Causes include decreased lung compliance from infiltrative disorders such as pulmonary fibrosis; reduced muscle strength from phrenic nerve injury, diaphragm dysfunction, or neuromuscular disease; pleural disease, including large pleural effusion or marked pleural thickening; and prior lung resection. The flow-volume loop combines the maximal expiratory and inspiratory flow-volume curves and is especially helpful in determining the site of airway obstruction. (See eFigure 9–1.0: illustration.) Lung Volumes, Capacities, and the Normal Spirogram The volume of gas in the lungs is divided into volumes and capacities as shown in the bars to the left of the figure below. Lung volumes are primary: they do not overlap each other. Tidal volume (VT) is the amount of gas inhaled and exhaled with each resting breath. Residual volume (RV) is the amount of gas remaining in the lungs at the end of a maximal exhalation. The vital capacity (VC) is the total amount of gas that can be exhaled following a maximal inhalation. The vital capacity and the residual volume together constitute the total lung capacity (TLC), or the total amount of gas in the lungs at the end of a maximal inhalation. The functional residual capacity (FRC) is the amount of gas in the lungs at the end of a resting tidal breath. (IC = inspiratory capacity; IRV= inspiratory reserve volume; ERV = expiratory reserve volume.) The forced vital capacity (FVC) maneuver begins with an inhalation from FRC to TLC (lasting about 1 second) followed by a forceful exhalation from TLC to RV (lasting about 5 seconds). The amount of gas exhaled during the first second of this maneuver is the forced expiratory volume in the first second (FEV1). Normal subjects expel approximately 80% of the FVC in the first second. The ratio of the FEV1 to the FVC (often referred to as the FEV1%) is diminished in patients with obstructive lung disease. It may be increased in patients with restrictive physiology. Modified, with permission, from Comroe JH et al: The Lung: Clinical Physiology and Pulmonary Function Tests, 2nd ed. Year Book Medical Publishers, 1962. eFigure 9–1.0. Representative spirograms (upper panel) and expiratory flow-volume curves (lower panel) for normal (A), obstructive (B), and restrictive (C) patterns. Spirometry is adequate for evaluation of most patients with suspected respiratory disease. If airflow obstruction is evident, spirometry may be repeated 10–20 minutes after an inhaled bronchodilator is administered. The absence of improvement in spirometry after inhaled bronchodilator in the pulmonary function laboratory does not preclude a successful clinical response to bronchodilator therapy. Measurements of lung volumes and diffusing capacity are useful in selected patients, but these tests are expensive and should not be ordered routinely with spirometry. Measurement of the single-breath diffusing capacity for carbon monoxide (DLCO), which reflects the ability of the lung to transfer gas across the alveolar/capillary interface, is particularly helpful in evaluation of patients with diffuse infiltrative lung disease or emphysema. The total pulmonary diffusing capacity depends upon the diffusion properties of the alveolar-capillary membrane and the amount of hemoglobin occupying the pulmonary capillaries. The diffusing capacity should therefore be corrected for the blood hemoglobin concentration.* *Corrected DLCO = Measured DLCO x where [Hb] is the measured hemoglobin concentration (g/dL). Elevated DLCO is observed in pulmonary hemorrhage and may be seen in acute congestive heart failure and asthma due to an increase in pulmonary capillary blood volume. Reporting the ratio of measured diffusing capacity to alveolar volume (DLCO/VA) is helpful, because a diminished diffusing capacity may only reflect a reduction in the breath taken during the maneuver. In patients with emphysema, the diffusing capacity is characteristically low, the alveolar volume normal or increased, and the DLCO/VA ratio is low. In patients with diffuse infiltrative lung disease, both the diffusing capacity and the alveolar volume are characteristically reduced, and the DLCO/VA ratio is normal or low. In patients with AIDS, DLCO is a highly sensitive screening test for the presence of pulmonary disease, especially Pneumocystis jiroveci (formerly P carinii) pneumonia, but it lacks specificity. A normal DLCO in an AIDS patient is strong evidence against Pneumocystis pneumonia. Arterial blood gas analysis is indicated whenever a clinically important acid-base disturbance, hypoxemia, or hypercapnia is suspected. Oximetry provides an inexpensive, noninvasive alternative means of monitoring hemoglobin saturation with oxygen. Oximeters monitor oxygen saturation and not oxygen tension. eFigure 9–1.1: illustration displays the normal relationship between oxygen saturation and partial pressure of oxygen in blood. This relationship is not linear. The clinical accuracy of pulse oximeters is reduced in such conditions as severe anemia (< 5 g/dL hemoglobin), the presence of abnormal hemoglobin moieties (carboxyhemoglobin, methemoglobin, fetal hemoglobin), the presence of intravascular dyes, motion artifact, and lack of pulsatile arterial blood flow (hypotension, hypothermia, cardiac arrest, simultaneous use of a blood pressure cuff, and cardiopulmonary bypass). Co-oximetry, a form of oximetry that uses additional wavelengths of light to identify oxyhemoglobin and deoxyhemoglobin, can identify the more common abnormal hemoglobins. The normal arterial PO2 falls with increasing altitude (eTable 9–1.0). eTable 9–1.0. The effect of altitude on PO2 in normal adults. Altitude (feet) Barometric Pressure (mm Hg) Atmospheric1 PO2 (mm Hg) Tracheal2 PO2 (mm Hg) Arterial3 PO2 (mm Hg) Sea level 760 159 149 99 2000 707 148 138 88 4000 656 137 127 77 6000 609 127 118 68 8000 564 118 108 58 10,000 523 109 100 50 15,000 426 90 80 30 1Dry gas. 2Saturated with water vapor. 3Actual values at altitude will be higher, depending on the degree of adaptation (ventilatory response to hypoxia). eFigure 9–1.1. Oxygen-hemoglobin dissociation curve, pH 7.40, temperature 38 °C. (Reproduced, with permission, from Comroe JH Jr et al: The Lung: Clinical Physiology and Pulmonary Function Tests, 2nd ed. Year Book Medical Publishers, 1962.) Nonspecific bronchial provocation testing may aid the evaluation of suspected asthma, when baseline spirometry is normal, and in unexplained cough. The subject inhales a nebulized solution containing methacholine or histamine. These agents cause bronchial smooth muscle constriction in asthmatic patients at much lower doses than in nonasthmatics. If the FEV1 falls by more than 20% at a dose of 16 mg/mL or less, the test is positive. Bronchial provocation testing is 95% sensitive for the diagnosis of asthma. A negative result therefore makes asthma unlikely. Specificity is lower—about 70%—since false positives may occur in several common conditions, including COPD, congestive heart failure, recent viral respiratory infection, cystic fibrosis, and sarcoidosis. Evans SE et al. Current practice in pulmonary function testing. Mayo Clin Proc. 2003 Jun;78(6):758–63. [PMID: 12934788] Miller MR et al. ATS/ERS Task Force. General considerations for lung function testing. Eur Respir J. 2005 Jul;26(1):153–61. [PMID: 15994402] Cardiopulmonary Exercise Stress Testing Cardiopulmonary exercise testing is usually performed to evaluate patients with unexplained exertional dyspnea. A bicycle ergometer or treadmill is used. Minute ventilation, expired oxygen and carbon dioxide tension, heart rate, blood pressure, and respiratory rate are monitored. The exercise protocol is determined by the indications for the test and the ability of the patient to exercise. Certain patterns of abnormal oxygen uptake or delivery can be identified and may lead to specific pulmonary or cardiac diagnoses. The test is also used to quantify cardiorespiratory capacity. Complications are rare. American Thoracic Society; American College of Chest Physicians. ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211–77. [PMID: 12524257]