Respiratory bronchiolitis-interstitial lung disease

History of present illness

A 61-year-old Caucasian man presented to the pulmonology outpatient clinic due to shortness of breath during exercise and nocturnal dyspnea. These symptoms had begun a few months earlier. He also had a cough with sputum almost every morning. However, he said that the cough did not bother him and considered it a normal consequence of cigarette smoking. A chest radiograph, prescribed by the general practitioner, showed a widespread reduced transparency of the lung fields with a slight reticulonodular pattern.

Past medical history

The patient was a retired bricklayer, current smoker of about 20 cigarettes a day, with a 47-pack-year history of smoking. He reported previous exposure to concrete dust. He denied exposure to organic agents such as birds and feathers nor to asbestos fibers. His family history was negative for pulmonary illness. He had no history of drug abuse, weight loss, or anorexia. He reported a transient ischemic attack a few years earlier. Since then, he was prescribed oral clopidogrel 75 mg once daily. On that occasion, he underwent a high-resolution computed tomography (HRCT) of the chest. However, this was not available at the time of the first pulmonology visit.

Physical examination and early clinical findings

At the time of the visit to the pulmonologist, the patient was afebrile (body temperature 36.7° C [98.06 °F]), alert, and cooperative. His body mass index was normal. Oxygen saturation measured by pulse oximeter (SpO ₂ ) was 95% on room air, heart rate was 85 beats/min, and blood pressure was 130/90 mm Hg.

Physical examination revealed inspiratory crackles on both lung bases. Moreover, a moderate increase in the convexity of the nail fold (finger clubbing) was noticed. He had no skin pallor, peripheral edema, or jugular vein distention. The patient denied Raynaud phenomenon, arthralgias, myalgias, sicca syndrome, or other symptoms suggesting a connective tissue disease. He admitted to having some daytime sleepiness since dyspnea disturbed his night rest.

Clinical course

The patient underwent pulmonary function tests that showed lung volumes within normal limits but with a slowing in the terminal portion of the spirogram (mid-flows) suggestive of an obstruction in small airways: forced expiratory volume in 1 second (FEV ₁ )/forced vital capacity (FVC) ratio was 71.5%, FEV ₁ was 90% predicted, FVC 94% predicted, forced mid-expiratory flow (FEF _25-75% ) 51% predicted, total lung capacity (TLC) 88% predicted, residual volume (RV) 96% predicted. A moderate reduction in the diffusion lung capacity was present (DLCO 60% predicted). The six-minute walk test (6MWT) on room air showed a normal walking distance without oxygen desaturation during exercise. At the overnight pulse oximetry test, oxygen levels were quite low but just sufficient (mean SpO ₂ 90.7%, > 88% for 99% of the time) and without fluctuations suggestive for sleep apnea. Blood tests showed no anemia nor polyglobulia, normal electrolytes, renal and hepatic function, and markers of inflammation. Testing for antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), and anti-neutrophil cytoplasmic antibodies (ANCA) were negative. The electrocardiogram and echocardiogram did not reveal signs of heart failure nor increase in pulmonary arterial pressure. The Mantoux tuberculin skin test (TST) was negative at 72 hours.

The HRCT of the chest ( Fig. 5.1 ) demonstrated a diffuse extensive bilateral parenchymal involvement, with multiple poorly defined centrilobular nodules, confluent ground-glass opacities, and some low attenuation areas. Abnormalities were slightly predominant in the subpleural regions of the upper-mid lung zones. Fine reticulation was evident in the subpleural lung parenchyma without traction bronchiectasis or bronchiolectases and any other signs of coarse fibrosis. The apical region of both lungs showed multiple clustered cysts of variable size, with regular thickened wall (<2 mm), compatible with airspace enlargement with fibrosis (AEF). Lung volumes appeared preserved. Diffuse bronchial wall thickening was also evident. The case was discussed by the interstitial lung diseases (ILD) multidisciplinary team.

The patient underwent outpatient bronchoscopy under mild sedation (midazolam 5 mg intravenous) and local anesthesia (topical lidocaine). On endoscopic evaluation, some areas of anthracosis were observed bilaterally in the bronchial mucosa. There were no alterations of bronchial patency or lesions suspicious of malignancy. A BAL was performed in the middle lobe with the instillation of 150 ml of saline solution (5 aliquots of 30 ml). BAL fluid differential cell count showed the presence of 91% macrophages, most of which characteristically exhibited brown pigments due to high exposure to cigarette smoke ( Fig. 5.2 ) BAL fluid culture was negative, no acid-fast bacilli (AFB) were identified, and cytological examination did not find any cells with malignant atypia.