Clinical History
A 58-year-old man presented with exertional dyspnoea. He was a former smoker (40 packs-years), had no professional exposure, no clinical signs of connective tissue disease and quit smoking 4 years ago. On physical examination he showed diffuse ronchi, velcro-like crackles on the lung bases, clubber fingers and cyanosis.
Imaging Findings
Chest X-ray demonstrated lower lobe reticular markings and upper lobe hyperlucency. High Resolution Computed Tomography (HRCT) was performed and showed predominantly upper lobe paraseptal bullae, small areas of low attenuation with ill-defined margins and without visible walls and lower lobe intra- and interlobular septal thickening, ground-glass opacities, traction bronchiectasis, architectural distortion and honeycombing.
The patient was also hypoxemic and underwent other instrumental investigations, namely spirometry [forced expiratory volume in one second (FEV1): 66%, forced vital capacity (FVC): 63%, FEV1/FVC: 84%, total lung capacity (TLC): 61%, transfer capacity of carbon monoxide (DLCO): 31%]; six-minute walking test (6MWT) in O2-6lt/min with decrease in arterial oxygen saturation (SpO2) from 97% to 79% (after 240mt O2-therapy was prescribed); bronchoalveolar lavage: 11% neutrophils, 1% eosinophils, 3% lymphocytes, 85% macrophages.
Discussion
The consensus definition of CPFE has been challenged; although initially considered to represent an incidental coexistence of two separate entities, CPFE has been recently proposed as a distinct syndrome. Its diagnosis is mainly based on HRCT findings and clinically is characterized by relatively preserved spirometric values and disproportionate impairment of gas exchange [1].
Its prevalence has been estimated between 5% and 10% of cases of interstitial lung diseases. It mainly affects men generally over 65 years of age, smokers or ex-smokers, so cigarette smoking is the main aetiologic factor.
Some mechanisms involved in the pathogenesis of CPFE have been reported: 1) increases in oxidative stress; 2) a mutation in the surfactant protein C gene in a young non-smoking female patient; 3) potential roles for TNF-a, IL-1/b, neutrophil elastase and metalloproteinases producing both emphysema and pulmonary fibrosis in animal models.
Some authors reported cases of CPFE in the absence of smoking or in the context of connective tissue diseases.
The main symptoms are: exertional dyspnoea, cough, wheezing, perioral cyanosis and asthenia. Physical examination reveals bibasilar inspiratory crackles and finger clubbing. The patients are at high risk for developing complications such as lung cancer, acute lung injury and pulmonary hypertension which has a dismal prognosis for their survival [1-3].
Chest X-ray can show reticular markings and upper lobe hyperlucency in both lung bases and subpleural regions but is neither sensitive nor specific in diagnosing CPFE. HRCT is the most appropriate investigation with these findings: 1) emphysema, defined as demarcated areas of low attenuation bordered by a very thin (<1mm) wall or without visible wall and/or subpleural bullae (>1 cm) predominantly in the upper lobes; 2) diffuse parenchymal disease with fibrosis defined as reticular opacities, honeycombing, traction bronchiectasis and/or bronchiolectasis predominantly in the lower lobes. Such findings correlate with histopathology: UIP is the most common pattern, but non-usual interstitial pneumonia, smoking-related ILD or even other unclassifiable fibrotic lung disease have also been observed [2-5].
Functional investigations as forced vital capacity, forced expiratory volume in the first second and total lung capacity are within normal ranges or slightly abnormal. Hypoxemia is moderate at rest and worsens during exercise. DLCO, the variable best correlated with the degree of parenchymal destruction, is reduced.
Treatment of CPFE is based on systemic corticosteroids, inhaled bronchodilators, immunomodulator drugs and oxygen therapy for hypoxaemia. Specific therapy for PHA has also been considered [1-3, 5].
Differential Diagnosis List
Combined pulmonary fibrosis and emphysema syndrome
Interstitial lung diseases secondary to inherited or acquired abnormalities
Interstitial lung diseases secondary to connective diseases
Final Diagnosis
Combined pulmonary fibrosis and emphysema syndrome
