Chronic Dyspnea Unexplained by History, Physical Examination, Chest Roentgenogram, andSpirometry* Analysis of a Seven-year Experience William} DePaso, M.D., F.G.G.R; Richard H. Winter-bauer; M.D., F.G.G.E }ames A. Lusk, M.D.; David F. Dreis, M.D., F.G.G.E; and Steven G. Springmeyer; M.D., F.G.G.E

The purpose of this article is to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to develop a logical diagnostic approach to such patients. Seventy-two consecutive physician-referred patients had dyspnea greater than one-month duration unexplained by the initial history, physical examination, chest roentgenogram, and spirometry. Patients underwent a standard diagnostic evaluation. A de6nite cause for dyspnea was recognized in 58 patients, and DO answer was found in 14. Twenty-two diseases were recognized in the patient group. Dyspnea was due to pulmonary disease in !6 (36 percent) patients, cardiac disease in ten (14 percent) patients, hyperventilation in 14 (19 percent) patients, and only 3 patients had extrathoracic disease causing dyspnea. Age younger than 40 years, intermittent dyspnea, and normal

alveolar-arterial oxygen pressure difference (P[A-a]OJ at rest breathing room air was strongly predictive of bronchial hyperreactivity or hyperventilation. No patient diagnosed as having disease of the lung parenchyma or vasculature had a P(A-a)O. s20 mm Hg. The differential diagnosis to explain dyspnea in patients with nondirective histories, normal 6ndings from physical examinations, DOrmal chest roentgenograms, and normal spirograms is extensive. The patient's age and measurement of gas exchange at rest help to formulate a diagnostic approach.

patients with chronic dyspnea will have M ostasthma, chronic obstructive lung disease, inter-

nondiagnostic chest roentgenogram; and (3) absence of spirometric evidence for either restrictive (FVC ~80 percent predicted normal) or obstructive (FEV/FVC 2:70 percent) lung disease. The chest roentgenogram was usually normal. In some instances there were minor roentgenographic abnormalities (focal parenchymal or pleural scarring, prominence ofpulmonary arteries, or plate-like atelectasiS) that were judged clinically insignificant because they were not an adequate explanation for the dyspnea and/or stable prior to and during the dyspnea. A flow-volume curve was performed with a spirometer (Ohio 840 or Wedge Med-Science 570) with a forced expiratory maneuver from maximal inhalation and analyzed according to the predicted normal values of Schoenberg et al. l

stitiallung disease, or cardiomyopathy diagnosed on objective findings from the histol"}; physical examination, chest roentgenogram, and spirometry.l Dyspnea that remains unexplained after this diagnostic seFor editorial comment see page 1187

quence provides a major diagnostic challenge. This report reviews our experience with 72 such patients seen over a seven-year period in a referral pulmonary practice. Our goals were to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to determine if a logical diagnostic approach could be formulated. METHODS

lbtient Population All physician-referred patients who presented to the section of Pulmonary and Critical Care Medicine of the Virginia Mason Clinic (Seattle, WA) between 1981 and 1988 with unexplained dyspnea of greater than one-month duration were prospectively enrolled in the stud~ Entry criteria included the following: (1) an unrevealing history and physical exmaination by the referring physician; (2) a ·From the Section of Pulmonary and Critical Care Medicine, the Virginia Mason Medical Center, Seattle, Washington. Manuscript received August 27; revision acceptea March 8. Reprint requests: Dr. Winterbauer, 1100 Ninth Avenue, Seattle, 98101

(Cheat 1991; 100:1293-99)

nco. =single breath carbon monoxide difFusion capacity; MlPI =maximal inspiratory and expiratory pressure; VIQ scan =ventilation-pelfusion lung scan


Diagnostic Evaluation

Each patient underwent a repeated history and physical examination. The history included age at onset, duration, pattern, and intensity ofdyspnea. The intensity ofdyspnea was graded according to the scale shown in 1llble 1. Patients in whom the repeated history and physical examination yielded previously unrecognized but diagnostically directive 6ndings were subjected to specific testing to confirm the impression reached. Patients with a negative history and normal results of a physical examination had a chemistry battery, including serum thyroxine level, and an arterial blood gas level at rest breathing room air with calculation of the alveolar-arterial oxygen gradient (P[A-a]OJ. The patients were then subjected to noninvasive testing. The tests used included the single-breath carbon monoxide diffusion capacity (Dcos.) analyzed according to Ogilvie et al, 3 repeat spirometry following inhaled bronchodilators, inspiratory flow-volume loop, measurement of maximal inspiratory and expiratory pressures (MIPIMEP), ventilation-perfusion lung scan (VIQ scan), a two-dimensional echocardiogram, cardiac exercise treadmill examination, Holter monitoring, methacholine or exercise bronchoprovocation testing, computed tomographic (Cf) CHEST I 100 I 5 I NOVEMBER, 1991


Table I-Grade of lJyspnea Grade



Dyspnea only with a vigorous exercise program" Dyspnea with walking on a steep hill without a load, walking up more than two flights of stairs, or carrying a moderate load while walking on the level Dyspnea with walking on a gentle hill without a load, walking up less than two flights of stairs, or carrying a light load while walking on the level Dyspnea with any walking on the level Dyspnea at rest Dyspnea of variable intensity


3 4 5


scanning of the thorax, upper gastrointestinal series, 24-hour esophageal pH monitoring, and cardiopulmonary exercise testing with measurement of gas exchange. The sequence and number of tests were performed at the discretion of the managing pulmonologist. The diagnostic sequence was terminated when a disease that offered an adequate explanation for the patient's dyspnea was recognized. No effort was made to perform all tests in all patients. Invasive tests such as fiberoptic bronchoscopy, open lung biopsy, and pulmonary or coronary arteriography were performed only when clinically indicated. Diagnostic Criteria For a disease to be accepted as the explanation for the patient's dyspnea, the follOwing criteria were met. (1) The diagnosis made had to be based on accepted diagnostic criteria. (2) The disease had to be a recognized cause of dyspnea and present in a degree consonant with the severity of the patient's dyspnea. (3) Whenever possible, treatment of the disease had to result in improvement or disappearance ofdyspnea. (4) A minimum one-year period offollowup failed to reveal any additional diseases capable of causing dyspnea. The diagnostic criteria for impaired oxygenation, bronchial hyperreactivity, and hyperventilation are listed in'Thble 2.4-7 Diagnostic criteria for other diseases recognized as causes of dyspnea are detailed and referenced in the CCResults" section. Patients who had no recognizable abnormality were classified as having unexplained dyspnea. Minimum testing in these patients included DcoSB , V/Q scan, and echocardiogram. In most instances, a more extensive evaluation was performed. In addition, a mean two-year follow-up failed to reveal any subsequent diagnoses that explained the dyspnea. At the completion of the study period, aU charts were reviewed by a single investigator (W J. D.) who was not involved in the patient's care, to ensure that diagnostic criteria were met. RESULTS

Seventy-seven patients were entered in the stud~ A repeat history and physical examination revealed previously unrecognized clinical findings that directed the diagnostic sequence in five patients. The presence of stridor led to the diagnosis of upper airway obstruction due to vocal cord paralysis in two patients. A patient with a chronic lower respiratory tract infection was recognized through a history of productive cough. One patient had typical angina pectoris and an endobronchial malignant neoplasm was recognized in one patient who had unilateral diminished breath sounds and palpable supraclavicular adenopath~ The remaining 72 patients with dyspnea unexplained by the 1294

pulmonologist's repeat history and physical examination, chest roentgenogram, and expiratory spirogram make up the final study group. Respiratory tract disease was the explanation for dyspnea in 26 (36 percent) patients, followed by cardiac disease in ten (14 percent), hyperventilation syndrome in 14 (19 percent), gastroesophageal reDux in three (4 percent), thyroid disease in two (3 percent), poor conditioning in two (3 percent), and renal disease in a single patient (Table 3). Fourteen patients (19 percent) had no recognizable cause of dyspnea. Respiratory Tract Disease

Bronchial Hyperreactivity: There were 12 patients with bronchial hyperreactivity. Inhalational or exercise provocation challenge tests were diagnostic in ten Table 2- DiGgnoBtic CriteritJ Diagnostic Criteria Impaired oxygenation at rest, breathing room air

Bronchial hyperreactivity

Hyperventilation syndrome

Reference PaOt 20 mm Hg (PaOI calculated using the alveolar gas equation assuming R=0.8 and Patm = 760 mm Hg) 1) ~15% increase in FEV. following inhaled isoproterenol, or 2) ~20% reduction in FEV1 during or within 20 minutes after exercise, or 3) ~20% decrease in FEV. at a methacholine concentration s8 mwml 4) beneficial response to bronchodilators 1) 5 or more of the following must be present: a) Episodic dyspnea; sudden in onset, brief in duration, and unrelated to exercise b) Palpitations c) Circumoral or peripheral paresthesias d) Inability to fill the lungs or take a satisfying breath e) Severe anxiety or fear associated with dyspnea f) Lightheadedness or dizziness g) Frequent sighing or yawning h) Trembling of the hands 2) Normal V/Q, DcoSB , and two-dimensional echocardiogram 3) Complete resolution of symptoms at last follow-up


5 6


Unexplained Chronic Dyspnea (DePeso et aI)

Table 3- Cause of DyIlpflelJ in 12 Patients Principal Organ System Involved (No. of Patients) Respiratory tract disease (26)

Anatomic Site of Disease (No. of Patients) Airway obstruction (14) Pulmonary parenchyma (5) Pulmonary vasculature (4) Respiratory muscles (2)

Cardiac disease (10)

Central nervous system (14) Thyroid

Chest wall (1) Myocardium (6) Conduction (2) Endocardium (1) Pericardium (1)

Kidney (1) Gastrointestinal tract (3) Poor conditioning (2) Unexplained (14)

patients. 5 ,6 The other two patients had an FEV I >80 percent of predicted normal but had > 15 percent increase in the FEV I after inhaled isoproterenol. All patients had a decrease in dyspnea with bronchodilator therap~

Intrathoracic Focal Large Ainvay Obstruction: One patient had a roentgenographically occult malignant neoplasm. The V/Q scan demonstrated absence of perfusion and ventilation to the affected lung. The diagnosis of endobronchial obstruction was confirmed by fiberoptic bronchoscopy. Surgical resection was successfully performed. Extrathoracic Upper Ainvay Obstruction: One patient had obstructive airflow disease due to bilateral vocal cord paresis. A flow-volume inspiratory loop suggested a variable extrathoracic obstruction and direct visualization demonstrated bilateral vocal cord dysfunction (immobile right cord and abductor paralysis of the left cord) with upper airway occlusion during rapid inspiration. 8 Bullous Disease: Bullous disease without spirometric evidence of airway obstruction was present in two patients. The diagnosis was established by visualization of bullae on both cr scan and pulmonary angiogram. Both patients were heavy smokers with DcosB

Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience.

The purpose of this article is to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to develop a logical diagnosti...
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