History of present illness
A 65-year-old man has been complaining of exertional dyspnea and dry cough for 2 years. During this period, he was treated with oral steroids, inhaled bronchodilators, and antibiotics without any improvement. He was initially identified as having a chronic obstructive pulmonary disease (COPD). Due to the clinical worsening, a chest radiograph was performed, which showed a basal reticular interstitial lung pattern ( Fig. 2.1 ). Therefore, the patient was referred to a pulmonologist.
Past medical history
The patient was a former smoker (40 pack-years) and a retired office worker, without significant occupational or environmental exposure to other noxious particles or gases. He had no family history of respiratory diseases. The only comorbidities were high blood pressure and type 2 diabetes mellitus for which he assumed antihypertensive therapy (valsartan) and oral hypoglycemic agents (glimepiride and metformin).
Physical examination and early clinical findings
At the physical examination, bilateral Velcro sounds were present in the lower fields of the lungs. Peripheral oxygen saturation (SpO 2 ) was 95% at rest in room air. The patient had no skin alterations, neither xerostomia nor xerophthalmia, no Raynaud phenomenon, nor other signs of connective tissue diseases (CTDs).
Clinical course
The presence, at the lower lobes of the lungs, of bilateral Velcro sounds, very specific for ILDs, suggested to the pulmonologists to deepen the diagnostic process by performing an HRCT of the lungs. This showed the typical radiological findings of a UIP pattern: peripheral reticulations, traction bronchiectasis, and honeycombing with a basal predominance ( Fig. 2.2 ; Fig. 2.3 ).
Pulmonary function tests ( Fig 2.4 ) revealed a restrictive lung pattern and a moderate reduction in diffusion capacity for carbon monoxide (DLCO).
Antinuclear antibodies (ANAs), extractable nuclear antigen (ENA) screening, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and the myositis panel were all negative. A rheumatological evaluation confirmed the absence of physical signs attributable to an underlying CTD. Specific serum IgG antibodies to various avian proteins, bacterial compounds, or molds (precipitins) resulted to be negative. The case was discussed by a dedicated multidisciplinary team (MDT) involving pulmonologists, radiologists, and rheumatologists.
Based on the available clinical and laboratory data, the MDT ascribed the UIP radiological pattern observed in this patient to IPF as no findings suggestive of another diagnosis were found.
At the 6-minute walk test (6MWT), the patient covered a distance of 350 m (67% predicted). He experienced severe dyspnea and had a significant oxygen desaturation after just 2 minutes (lowest SpO 2 = 86%, mean SpO 2 = 90.6%).
The patient also underwent overnight pulse oximetry, which showed nocturnal hypoxemia with a mean SpO 2 of 89.8% and a small number of desaturations per hour of sleep (oxygen desaturation index [ODI] was 34.6). Overall, the patient spent 29.4% of the night with SpO 2 < 90%. The lowest value of SpO 2 was 81%.
Echocardiography revealed mild mitral and tricuspid regurgitation with preserved systolic function and no significant increase in pulmonary artery pressure.
Recommended therapy and further indications
When the diagnosis of IPF was made, the pulmonologist explained to the patient the opportunity to start an antifibrotic therapy. The patient accepted this advice. The physicians did not find drug interaction or other comorbidities that can preclude nintedanib or pirfenidone prescription. Therefore, they shared this important decision with the patient and explained the possible side effects of such drugs and their frequency. During the discussion, the patient expressed concern about photosensitivity, which occurs in about one out of three patients during treatment with pirfenidone. Conversely, he didn’t care about diarrhea, which is more common when taking nintedanib. Thus, nintedanib 150 mg, 1 pill after breakfast and 1 pill after dinner was started. Monthly laboratory tests (complete blood count, direct and total bilirubin, transaminase, γ-glutamyl transpeptidase, and serum creatinine) were scheduled.
Unfortunately, the drug intake was temporarily stopped for a significant alteration of transaminases after about 3 months. The pulmonologists waited for normalization of these parameters and started again with a lower dosage of the same drug, nintedanib 100 mg twice daily. Oxygen supplement during sleep and effort was recommended. Further echocardiography was scheduled to assess the presence of arterial hypertension.
Follow-up and outcomes
After approximately 1 year of follow-up, symptoms were relatively stable, as well as lung volumes and diffusion capacity. In detail, the forced vital capacity was 73% predicted, and DLCO was 50% predicted. The new chest HRCT revealed no signs of radiological progression. The extent of reticulation and honeycombing was approximately the same. No ground-glass opacities or other alterations that might suggest acute exacerbation emerged. The mean pulmonary arterial pressure estimated by echocardiography was near the upper limit of normal (25 mmHg).
