Histopathology and Exercise: A Winning Combination in Pulmonary Fibrosis: A Case Report

Case Report

In July 2006, a 50-year-old white man presented to us with non-productive cough and dyspnea, which had recently started and were accentuated by exercise. He had no fever, chest pain, hemoptysis, weight loss, nor appetite loss. He was a smoker (35 pack-years) and had a family history of COPD and high blood pressure. He worked as land surveyor and had an unremarkable medical history. He was a highly practiced runner, who ran 8 km, in 1 hour, 4 times a week. He had no pets at home, especially birds, and no past asbestos exposure. Physical examination disclosed bilateral finger clubbing and post-tussive “Velcro” crackles at both lung bases.

Laboratory studies revealed elevated erythrocyte sedimentation rate (37 mm/h, normal value < 15 mm/h) and C-reactive protein (13.7 mg/L, normal range 0–5 mg/L), but rheumatoid factor, anti-nuclear antibodies, anti-neutrophilic cytoplasmic antibodies, double-stranded DNA antibodies, and extractable nuclear antigens were all in the normal range.

His baseline pulmonary function test results were all in the normal range (Table 1). In a 6-min walk test he walked 663 m, at the end of the test his Borg dyspnea score was 1.5, and he had no important S_pO2 decrease during the test (Table 2). But in a maximal cardiopulmonary exercise test he had a substantial P_aO2 decrease, from 81 to 69 mm Hg (see Table 2).

HRCT showed increased peripheral reticular markings, especially at the lung bases, with honeycombing and diffuse thickening of the alveolar septa.

Bronchoscopy was unremarkable. Bronchoalveolar lavage fluid revealed no malignant cells, and a CD4/CD8 T lymphocytes ratio of 0.9 (range 1.3–2.3). The bronchoalveolar lavage fluid was negative on both microscopy and culture for bacteria, fungi, and mycobacterium. Surgical biopsy of the right upper and lower lobe showed predominant features of nonspecific interstitial pneumonia, with a rather uniform fibrosing pattern and associated lymphoid follicles, but without fibroblastic foci.

On the basis of the laboratory, histopathology, and radiologic results, the diagnosis was nonspecific interstitial pneumonia with fibrosing pattern. We promptly initiated oral prednisone: 1 mg/kg of body weight, daily for 12 weeks, then tapered over 6 weeks, then stopped. There were no important adverse effects.

After the first few weeks of treatment he experienced marked improvement in cough and exercise dyspnea, resumed his exercise training, and within a few months reached almost the same intensity exercise he had before the symptoms arose. HRCT 6months after the end of treatment was substantially unchanged, and showed only mild ground-glass attenuation and patchy consolidation.

In December 2010, following 4 years of well-being, during which he continued his usual exercise training, he presented with persistent cough, severe dyspnea at rest, and fever, and urgently hospitalized. On admission laboratory blood tests showed neutrophilic leucocytes and elevated erythrocyte sedimentation rate (56 mm/h) and C-reactive protein (226 mg/dL). Pulmonary function tests revealed a moderate restrictive defect, a severe reduction in diffusing capacity of the lung for carbon monoxide, and severe hypoxemia. Blood gases analysis showed metabolic alkalosis (pH 7.48, P_CO2 38.5 mm Hg, HCO₃ 27.9 mmol/L) (see Table 1). His 6-min walk test was 295 m and during the test he desaturated from 89% to 81% (see Table 2).

Doppler echocardiography demonstrated enlargement of the right atrium and ventricle, with a systolic right ventricular pressure of 45 mm Hg. Left ventricular systolic and diastolic function was in the normal range.

HRCT chest revealed increased reticular markings, widespread bilateral, asymmetrical patchy areas of ground glass attenuation with basal predominance, and thickened bronchovascular bundles in the basal fields of both lungs.

The diagnosis was exacerbation of nonspecific interstitial pneumonia, and he was started on intravenous glucocorticosteroids (methylprednisolone, 5 mg/kg daily), intravenous antibiotics (meropenem, voriconazole, and levofloxacin), intravenous diuretics, and oral N-acetylcysteine.

After 2 weeks the exacerbation resolved and he began a 5-week pulmonary rehabilitation program, including respiratory-muscle exercise training and upper and lower limb muscle training. Daily sessions included low-weight, high-repetition arm cycle ergometer training (30 min), treadmill walking (30 min), and bicycle training (30 min). He also attended 1-hour educational classes 3 times a week. After rehabilitation he had consistent improvements in symptoms, lung function, and exercise tolerance (see Table 1), and since December 2012 (as assessed via periodic telephone interviews) he has been asymptomatic at rest and continues his exercise, walking 1 hour a day, 3 times a week, with supplemental oxygen at 1 L/min, although, as would be expected, at a lower intensity than before the symptoms arose.