REVIEW Evaluation of wheezing in the nonasthmatic patient DAVID A. HOLDEN, MD AND ATUL C. MEHTA, MD • Wheezing is a nonspecific manifestation of airway obstruction. Even though bronchial asthma is the most common cause of wheezing, a variety of pulmonary and nonpulmonary conditions can present with this symptom. In recent years methacholine provocation challenge has simplified detection of bronchial asthma; however, establishing accurate diagnosis of other causes of wheezing is important because each condition requires specific treatment. This article describes a methodical approach to the diagnosis of wheezing in patients who are not asthmatic. • INDEX TERMS: WHEEZING, AIRWAY OBSTRUCTION, BRONCHIAL ASTHMA • CLEVE CLIN J MED 1990; 57:345-352 IRTUALLY ANY PROCESS that involves HISTORY the tracheobronchial tree can produce wheezing, which is a nonspecific manifesta- Three issues need special attention in the history: the tion of airway obstruction. Causes of wheez- age at onset, the nature of the onset, and the course of Ving in the nonasthmatic include upper airway condi- symptoms. tions such as angioedema, lower airway conditions such as chronic obstructive pulmonary disease (COPD), Age at onset vascular causes such as pulmonary embolism, and un- The prevalence of bronchial asthma in children and usual causes such as carcinoid syndrome or factitious adults is comparable.1 Although it is the most common asthma (Table I ). It is important to differentiate these cause of wheezing in children, diagnostic confirmation is conditions, because their treatments vary. This article often difficult and empiric treatment is frequently insti- presents a practical approach to the diagnosis of wheez- tuted. ing in patients who are suspected not to be asthmatic. Wheezing in infants may signal the presence of con- Often these patients have failed to respond to aggressive genital anomalies such as vascular rings, bronchopulmo- asthma treatment or have negative provocation chal- nary dysplasia, or bronchomalacia. In addition, cystic fi- lenge tests for bronchospasm. brosis can present as recurrent wheezing during childhood; a sweat chloride test may be indicated when wheezing is accompanied by gastrointestinal complaints or a suggestive family history.2 Foreign body aspiration may cause wheezing in child- From the Department of Pulmonary Medicine, The Cleveland ren, especially between 6 months and 3 years of age. Clinic Foundation. Foods are the substances most commonly aspirated, and Address reprint requests to A.C.M., Department of Pulmonary 3 Medicine, The Cleveland Clinic Foundation, One Clinic Center, in most cases a history of aspiration is obtainable. 9500 Euclid Avenue, Cleveland, Ohio 44195. Aspiration of large foreign bodies into the esophagus JUNE 1990 CLEVELAND CLINIC JOURNAL OF MEDICINE 345 Downloaded from www.ccjm.org on September 23, 2021. For personal use only. All other uses require permission. WHEEZING IN THE NON ASTHMATIC PATIENT • HOLDEN AND MEHLA TABLE 1 Wheezing is heard in 2% of patients with bronchogenic DIFFERENTIAL DIAGNOSIS OF WHEEZING carcinoma; often the tumor is centrally located, causing UPPER AIRWAYS compression of a large bronchus or, rarely, of the tra- Vocal cord paralysis chea.5 Endobronchial metastasis from such malignancies Laryngeal neoplasms Subglottic stenosis as colon, renal, or thyroid carcinoma, seminoma, or Foreign body melanoma may result in obstruction.6 Infection Vincent's angina Diphtheria Nature of onset Epiglottitis Patients with acute onset of wheezing should be ques- Laryngeal edema Angioedema tioned about prior episodes and response to therapy. A Burns history compatible with aspiration, left ventricular Systemic lupus erythematosis failure, pneumonia, pulmonary embolism, or anaphy- Laryngeal spasm Infection laxis should be sought. Recognition of risk factors for Tetany these conditions, such as a seizure disorder or alcoholism Psychogenic Laryngomalacia in aspiration pneumonia and prior surgery or prolonged Laryngeal web bedrest in pulmonary embolism, leads to appropriate di- LOWER AIRWAYS agnostic testing. Bronchial asthma COPD (emphysema, chronic bronchitis) The aspiration of gastric juices during the induction Infections of anesthesia was first described by Mendelson.7 It was Pyogenic Tuberculosis invariably associated with the acute onset of wheezing, Fungal but subsequent infection was infrequent. The sputum Aspiration produced by these patients can be pink and frothy, simi- Foreign body (esophagus) Cystic fibrosis lar to that seen in pulmonary edema. Tracheal stenosis, tracheomalacia Other predisposing conditions may result in aspira- Tracheal web tion. In fact, most patients with aspiration pneumonia Mediastinal masses/lymphadenopathy Allergic bronchopulmonary aspergillosis have an identifiable risk factor. In one study, more than Parasitic infestations 90% of such patients had a predisposing cause: for ex- Lo filer's syndrome Bronchiolitis ample, 24% had aspirated around a nasogastric tube, Bronchiectasis 39% had a motility disturbance of the esophagus, and Chemical bronchitis 29% had a history of impaired consciousness.8 Endobronchial sarcoidosis Endobronchial amyloidosis Pulmonary embolism may manifest itself as wheezing Bronchopulmonary dysplasia and tachypnea alone. Although 85% of patients with VASCULAR Cardiac asthma angiographically proven pulmonary embolism in one Pulmonary embolism series had a decrement in FEVu few had audible wheez- Vasculitis ing.9 A predisposing factor for embolization is identified Polyarteritis nodosa (PAN) Allergic in more than 90% of all patients with pulmonary em- Primary pulmonary hypertension bolism.10 Patients who wheeze with pulmonary em- Vascular rings bolism often have a history of childhood asthma or an Subglottic hemangioma 11 OTHER allergic diathesis. Serotonin and histamine release Carcinoid syndrome from platelets, regional hypoxia, and hypocarbia all play Factitious a role in bronchoconstriction of the terminal airway in this condition.12 Pulmonary embolism must be con- sidered in an adult with wheezing and signs and symp- such as coins, buttons, tacks, or bone can cause wheez- toms of right heart failure or lower extremity venous ab- ing due to pressure on the airway. Adults may aspirate as normalities.13 well. In one review, 40% of the patients with esophageal The insidious onset of wheezing, particularly if as- foreign bodies were adults; meat and bone fragments sociated with hemoptysis or hoarseness, may suggest were the objects most often aspirated.4 bronchogenic carcinoma, tracheal tumor, or endo- Although asthma can present at any age,1 the onset of bronchial metastasis. In the adult, the most common wheezing in a patient over age 40, particularly if it is lo- tracheal tumors are squamous cell carcinoma and ade- calized, may be due to an intraluminal neoplasm. noid cystic carcinoma.14,15 346 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 57 NUMBER 4 Downloaded from www.ccjm.org on September 23, 2021. For personal use only. All other uses require permission. WHEEZING IN THE NONASTHMATIC PATIENT • HOLDEN AND MEHTA Clinical course ting and supine auscultation. Wheezes were heard in 48 The clinical course of wheezing can be categorized as of the 83 patients with obstruction. None of these intermittent, persistent, or progressive. Patients with showed a significant response to bronchodilators. Forced emphysema or chronic bronchitis may complain of expiratory wheezing bore no relation to the extent of ob- either persistent or intermittent wheezing; these pa- struction or to response to bronchodilator therapy. tients are older and have a significant smoking history. Wheezes were heard only in the supine position in 11 of Progressive wheezing associated with a history of al- the 48 patients. lergic rhinitis, skin lesions, and abdominal pain is Some clues to the source of wheezing in the nonasth- characteristic of the Churg-Strauss syndrome.16 The dis- matic patient may be gained from the head and neck ex- ease may be diagnosed as asthma initially, but the amination—for example, signs of upper respiratory tract development of severe eosinophilia, pulmonary infil- infection, lymphadenopathy, thyromegaly, a scar from trates, and vasculitis identifies the syndrome. prior tracheostomy, and jugular venous distention. A more fulminant course is seen in patients with id- Other significant signs include an absent gag reflex in a iopathic hypereosinophilic syndrome, 40% of whom patient who aspirates, and the lip and tongue swelling of have pulmonary involvement manifested by bron- angioedema. Skin findings should be noted, such as the chospasm and pulmonary infiltrates.17 A restrictive car- palpable purpura of vasculitis, the waxy papules of amy- diomyopathy often develops from eosinophilic infiltra- loidosis, the linear erythema of visceral larva migrans, tion. the flushing of carcinoid syndrome, or the venous con- Diseases associated with intermittent wheezing most gestion of deep vein thrombosis. closely resemble bronchial asthma. Left ventricular dys- The presence of clubbing is important. Conditions function is a common imitator. An older patient with that cause both clubbing and wheezing include bron- wheezing and a history of angina pectoris, myocardial chogenic carcinoma, congenital heart disease, and cystic infarction, or hypertension should be questioned about fibrosis. Holsclaw22 submits that asthma and clubbing in dyspnea, orthopnea, and pedal edema. Interstitial edema young adults are incompatible diagnoses. Bronchiectasis and vascular