Wheezing in a 52-Year-Old Woman With a History of Colon Cancer

April 1, 2006

A 52-year-old woman was admitted tothe hospital with progressive shortnessof breath of 2 days’ duration. Bronchialasthma had been diagnosed 6 monthsearlier; inhaled corticosteroids, bronchodilators,and leukotriene antagonistswere prescribed. Despite aggressivetreatment, the patient’s dyspneaand wheezing worsened.

A 52-year-old woman was admitted tothe hospital with progressive shortnessof breath of 2 days' duration. Bronchialasthma had been diagnosed 6 monthsearlier; inhaled corticosteroids, bronchodilators,and leukotriene antagonistswere prescribed. Despite aggressivetreatment, the patient's dyspneaand wheezing worsened.

The patient denied allergy, fever,chills, rigors, hemoptysis, and chestpain. She did not smoke cigarettes oruse alcohol. Three years earlier, shehad undergone surgery for colon cancer;the patient has had no recurrences,and there are no known metastases.

The patient was in obvious distress;respiration rate was 26 breathsper minute with the use of accessorymuscles. She was afebrile; pulse ratewas 88 beats per minute; blood pressure,120/80 mm Hg. No clubbing orcyanosis was noted. Heart sounds werenormal and without murmurs. Bilateralwheezing, which was more prominenton the right side, was heard onauscultation. The abdominal andneurologic examination findings wereunremarkable.

White blood cell count was11,200/μL with 72% neutrophils, 21%lymphocytes, and 7% monocytes. Hemoglobinlevel was 12.7 g/dL; hematocrit,32%. The blood gases on roomair were pH, 7.44; PCO2, 30 mm Hg;and PO2, 72 mm Hg. Forced vitalcapacity (FVC), 96% of predicted;forced expiratory volume in 1 second(FEV1), 72% of predicted; andFEV1:FVC ratio, 65. There was nosignificant bronchodilator response.The carbon monoxide-diffusing capacitywas 72% of predicted.

A chest film revealed hyperinflationon the right side (Figure 1); infiltrate,effusions, and lymphadenopathy wereabsent. Because of the unilateral wheezingand the failure of conventional antiasthmamedication, a bronchoscopywas performed. The procedure demonstrateda normal trachea and normalleft main bronchus; however, an endobronchialpolypoidal lesion was foundon the right main stem bronchus (Figure2). A brush biopsy of the lesion revealeda poorly differentiated adenocar-cinoma that was most likely a metastaticlesion arising from the prior coloncancer.Following resection of the tumor,the patient's wheezing and dyspneamarkedly improved.

DIFFERENTIALDIAGNOSIS
Keep in mind that "all thatwheezes is not asthma."1 As in thispatient, endobronchial lesions thatcause airway obstruction may be misdiagnosedas asthma. This case offersclues and strategies to help youdifferentiate between asthma andother causes of wheezing.

Asthma. The differential diagnosisof asthma is one of the mostdifficult problems in clinical medicine.Although traditionally asthmaconjures images of paroxysms ofwheezing, shortness of breath, andcough, the disease's presentationcan be deceptive. Asthma may presentas uncontrolled cough or dyspneaalone; most patients havewheezing as well.

Wheezing is usually absentwhen the asthmatic process is in remission.It is occasionally absent insevere attacks, presumably becausethe patient is not able to generate sufficientairflow velocity to producewheeze. Conversely, wheezing maybe a prominent manifestation of numerousnonasthmatic conditions ofthe lung (Table 1). These pseudoasthmaticsyndromes respond poorlyto standard antiasthma therapy;however, specific therapy directedat the underlying disease is oftenhighly effective.

 Table 1 –Differential diagnosis of wheezing and dyspnea
Bronchial asthma Nonasthmatic diseases      AIDS      Angioedema      Bronchiolitis      Carcinoid syndrome      Central airway obstruction      Chronic obstructive pulmonary disease      Cocaine toxicity      Congestive heart failure      (“cardiac asthma”)      Endobronchial tuberculosis      Environmental and industrial toxins (eg, smoke inhalation)      Factitious asthma      Gastroesophageal reflux      Laryngeal dysfunction      Microvascular angina      Psychosomatic illness      Pulmonary embolism      Sarcoidosis Pulmonary infiltration with eosinophilia      Allergic bronchopulmonary aspergillosis       Chronic eosinophilic pneumonia       Churg-Strauss syndrome       Löffler syndrome      Tropical pulmonary eosinophilia 

Other causes of wheezing.
Wheezing and shortness of breathindirectly indicate airflow obstruction.The patency of the airways andthe maintenance of laminar flow dependon a variety of related forces,including the tone of the bronchialmusculature, the integrity of the supportingcartilage, and the amountand character of secretions. A derangementof any of these factorsmay result in wheezing. For example,in patients with congestive heartfailure, edema of the mucous membranecan greatly narrow the caliberof the airway, causing so-called cardiacasthma, or left ventricular failuremanifested by wheezing and dyspnea.Similarly, pulmonary embolicdisease may induce the release ofbronchoactive amines that affect thetone of the tracheobronchial treeand occasionally produce diffusepolyphonic wheezing. Cocaine toxicityalso may present with wheezingthat is caused by cocaine-inducedbronchial muscle contraction.

Pulmonary infiltration witheosinophilia. All pulmonary infiltrationwith eosinophilia (PIE) syndromesfeature pulmonary infiltration and peripheralblood eosinophilia. Asthmalikesymptoms, particularly wheezing,may be prominent in the followingPIE disorders:

  • Lffler syndrome, a self-limited diseasethat features transient pulmonaryinfiltrates and eosinophilia associatedwith helminthic infection.
  • Chronic eosinophilic pneumonia,which is characterized by severe respiratorydistress that includes wheezing,fever, night sweats, weight loss,and eosinophilia. Dense infiltrates ina peripheral distribution are usuallynoted on chest films.
  • Tropical pulmonary eosinophiliapresents with cough, dyspnea, andwheezing and may occur in patientswith filarial infection.
  • Allergic bronchopulmonary aspergillosisis a complicated or a specialform of asthma in which the immunologicreactions to Aspergillus speciesplay an important role.
  • Churg-Strauss syndrome predominatelyinvolves the lungs and manifestswith eosinophilia, granulomatousreactions, and usually severe asthma.

Vocal cord dysfunction. This syndromeis characterized by episodes ofwheezing that are precipitated bystress or infection. The wheezing usuallyis produced by vocal cord adductionduring inspiration. Often seen inyoung women, this condition can bediagnosed by laryngoscopy.

Cancer of the lung. Pulmonarymalignancy has many and variedpresentations; wheezing is a presentingcomplaint in up to 2% of patients.2 Wheezing occurs more frequentlywith hilar tumors, whichcause narrowing of large bronchi;with polypoidal endobronchial lesions;or with a combination of bothtumors. Bronchial carcinoids andpapillomas,3,4 endobronchial sarcoidosis,and broncholiths havebeen associated with wheezing.

 Table - Causes of central airway obstruction
Site Possible cause

Larynx Vocal cord palsy Epiglottitis Tumor Polyp Spasm

Extrinsic trachea Mediastinal tumor Aortic aneurysm Goiter Hematoma

Intrinsic trachea Stricture Tracheomalacia Endobronchial disease (lung cancer, metastasis)

Central airway lesions. Table 2lists a number of lesions that cancause complete or partial airflow obstructionin the large airways. Theclinical manifestations include intermittentwheezing that frequently isassociated with terrifying episodesof stridor and severe spasms ofcoughing. In addition, an irritatingreflex mechanism of focal central lesionsmay induce diffuse bronchoconstrictionthat results in widespreadpolyphonic wheezing. Symptomsusually occur with exercise,when the airway diameter is reducedto about 8 mm. Pedunculatedlesions may cause position-relatedsymptoms that are suggested by theoccurrence of unilateral or diffusewheezing when the patient is recumbent.Most central airway lesionsthat are associated with wheezingrequire surgical therapy.

Metastatic disease. Endobronchialmetastases from nonpulmonarytumors, such as seen in this patient,are rare but must always be consideredin the differential diagnosis. Thecommon primary sites include breast,colon, and kidney. Clinically significantlesions that cause symptoms oflarge airway obstruction or hemoptysisoccur infrequently--probably infewer than 5% of patients with extrathoraciccancers.5

Nonallergic or mechanical. Anumber of clues to a nonallergic ormechanical cause of wheezing havebeen reported.6 These include thesudden onset of wheezing; a historyof aspiration; nocturnal asthma alone;the absence of allergic markers, suchas a history of atopy, hay fever, oreczema; the absence of a specific triggeringmechanism or cause; a fairto poor response to bronchodilatortherapy; and the presence of othersigns of associated diseases, such asfever, hemoptysis, or cellulitis of theneck.

DIAGNOSTIC STUDIESRadiography. The chest films ofpatients with wheezing may be normal.When a central lesion is present,the radiograph often will demonstratesigns of bronchial obstruction, suchas segmental and lobar atelectasiswith or without postobstructive pneumoniaor distal consolidation. Rarely,a ball-valve effect of an obstructingtumor may cause distal air trappingand a distal hyperlucent lung,7 as wasseen in this patient. A unilateral hyperlucentlung field can be visualizedin patients with bronchial asthma;this may be produced by mucousplugs that can suddenly block thecentral airway and lead to worseningdyspnea.8

Bronchoscopy. Results of bronchoscopyare definitive and providean anatomic and pathologic diagnosis.

Other studies. Plain film tomographymay reveal an endobronchialmass. Thin-section CT scans offerbetter diagnostic information; theyhelp localize the tumor and may provideinformation regarding associatedlymphadenopathy. Evaluation of theflow-volume loop may offer a clue tothe diagnosis.9

References:

REFERENCES:1. MacDonnell KF, Beauchamp HO. Differential diagnosisof asthma. In: Weiss EB, Stein M. BronchialAsthma: Mechanisms and Therapeutics. 3rd ed.Boston: Little, Brown and Company; 1993:459-484.
2. Hyde L, Hyde CI. Clinical manifestations of lungcancer. Chest. 1974;65:299-306.
3. Dipaolo F, Stull MA. Bronchial carcinoid presentingas refractory asthma. Am Fam Physician. 1993;48:785-789.
4. Abdullah AK, Danial BH, Zeid A, et al. Solitarybronchial papilloma presenting with recurrent dyspneaattacks: case report with computed tomographyfindings. Respiration. 1991;58:62-64.
5. Braman SS, Whitcomb ME. Endobronchialmetastasis. Arch Intern Med. 1975;135:543-547.6. Leape L. Surgical causes of asthma. In: BermanBA, MacDonnell KF, eds. Differential Diagnosis andTreatment of Pediatric Allergy. Boston: Little, Brownand Company; 1981:117-128.
7. Mak H, Metz SJ, Stokes DC, et al. Recurrentwheezing and massive atelectasis in an adolescent.J Pediatr. 1983;102:955-962.
8. Niederman MS, Gambino A, Lichter J, et al. Tensionball valve mucus plug in asthma. Am J Med.1985;79:131-134.
9. Gold WM. Pulmonary function testing. In: MurrayJF, Nadel JA, eds. Textbook of Respiratory Medicine.Philadelphia: WB Saunders Company; 1994:798-900.