A case of idiopathic pulmonary fibrosis

A 64-year-old female patient complaining of cough with scarce yellowish sputum, severe exertional dyspnoea and weakness in the last 3 weeks and treating with aminopenicillins and ipratropium bromide+fenoterol for 7 days with minimal effect. Her lung function had progressively deteriorated during last 2 years. She had stopped smoking 6 years ago.
Clinical examination revealed dyspnoea and tachypnoea with multiple predominantly bibasal crackles, O2 saturation was 85%, restrictive changes were identified at spirometry.

Inspiratory chest CT showed inhomogeneous decrease of pneumatisation, multiple foci of irregularly spaced reticulation, honeycombing pattern (clustered cystic air spaces of variable diameters, occasionally up to 15 mm, with thick, dense walls) and traction bronchiectasis. The latter is defined as irregular bronchial dilatation surrounding retractile pulmonary fibrosis. It is important that all the reticular abnormalities are predominantly in subpleural zones and there is craniocaudal gradient of the lesions, seen on coronal images.
Also sliding hiatal hernia (no contrast enema was given) is observed.
Described features are consistent with usual interstitial pneumonia (UIP) pattern. Considering the appropriate anamnesis and clinical findings, idiopathic pulmonary fibrosis (IPF) was diagnosed.

Background
IPF is a chronic, progressive, fibrotic interstitial lung disease of unknown cause [1]. Repeated alveolar micro-injury superimposed on pro-fibrotic epigenetic reprogramming, impaired mechanisms of alveolar epithelium repair and dysfunction of surfactant leads to development of fibrosis [3-5].
IPF requires differentiation with alternative causes of pulmonary fibrosis, preferentially with connective tissue disorders (e.g. rheumathoid arthritis, antisynthetase and Sjogren's syndromes), chronic hypersensitivity pneumonitis, occupational lung diseases and drug toxicity [1,2].

Clinical Perspective
A diagnosis of IPF requires multidisciplinary discussion among clinician, radiologist, pathologist and other specialists if it’s needed (e.g. in cases of connective tissue disorders suspected). Especially when clinical history or radiological patterns are not definite. A diagnostic search begins with clinician’s work, who has to establish a probability of interstitial lung diseases (ILD) presence and exclude their known causes like occupational exposure, connective tissue disorders, drug addiction. The probability of the diagnosis is increased in male patients, smokers, over 60 y/o with a family history of ILD and/or comorbid lung pathology [1,2,6].
Physical examination can reveal unexplained exertional dyspnoea, progressing with time, chronic dry cough, fine high-pitched bibasilar inspir¬atory crackles (so called velcro-like sounds).
Spirometry typically detects restrictive changes and plethysmography - a reduction in diffusing capacity of the lung for carbon monoxide [1,2,5].
In our case, a diagnosis of IPF was proposed at the stage of clinical examination due to the anamnesis and clinical findings. Although in a differential list, there was also pneumonia, chronic bronchitis and COPD.
After revising CT results according to ATS/ERS guidelines, serological testing was provided, and connective tissue diseases were excluded.

Imaging perspective

High-resolution CT protocols are required with the thinnest collimation and should include both inspiratory and expiratory images.
All consequences of pathophysiologic processes can be clearly seen on chest CT. Fibrotic changes implicate interstitium inside the secondary pulmonary lobule, which appears on CT as intralobular reticular pattern with irregular thickening of the interstitium. Because of aberrant alveolar repair and continuous micro-injuries, acinar structure is completely destroyed and alveoli become deformed. They evolve into cysts of different sizes and shapes, surrounded by walls of variable thickness. In total all these changes are named as honeycombing pattern.
Patchy, basal subpleural predominant distribution of honeycombing, fit by presence of reticular abnormalities, traction bronchiectasis or bronchioloectasis represents UIP pattern. In some cases, these lesions may be associated with ground glass opacity (GGO). If all features of UIP except for honeycombing are presented, such pulmonary lesion is regarded as probable UIP pattern. In both cases definite diagnosis of IPF can be made, considering appropriate anamnesis (patients over 60 years, smokers, with progressive deterioration of lung function, absence of other potential causes of ILD) and clinical data (worsening of dyspnoea, cough with sputum, restrictive changes at spirometry). When there is no strong evidence of UIP pattern – only subtle reticulation with basal subpleural predominant distribution and probable mild GGO is presented, intermediate for UIP pattern should be assigned. In such cases, and when an alternative diagnosis is suggested, a biopsy is required [1,2,4,5]. Although according to ATS/ERS guidelines even in cases of probable UIP pattern with inappropriate anamnesis and clinical data biopsy is recommended [6].
In the described case there are quite extensive areas of GGO, which match up with honeycombing distribution and aren’t as pronounced as reticulation abnormalities. Such changes may be regarded as demonstration of fibrotic changes and as sign of infection. The letter is more probable in our case in the background of clinical examination.

Treatment
As first-line therapy, Nintedanib e.g. pirfenidone, having a number of anti-inflammatory and antifibrotic effects, are recommended [1 3-5].
Several options for non-pharmacologic treatment are available: smoking cessation, supplemental oxygen therapy, administration, special complex of pulmonary rehabilitation exercises, and age-appropriate vaccines [1,4,5].

Take home massages:
1.    At least brief knowledge of IPF pathogenesis is crucial for understanding the nature of pathologic findings from the CT image.
2.    Since IPF has no single pathognomonic feature, it should be diagnosed based on complex assessment of anamnesis, symptoms, chest CT data and pathologic findings.
3.    In cases of typical or probable UIP patterns, considering exact IPF anamnesis and clinics, no biopsy is required for diagnosis.

Written informed patient consent for publication has been obtained.