A Rare Case of CPFE Syndrome: An Unacknowledged Entity

ABBREVIATIONS USED IN THIS ARTICLE

ABG = Arterial blood gas; BMI = Body mass index; CPFE = Combined pulmonary fibrosis with emphysema; DLCO = Diffusing capacity of the lungs for carbon monoxide; FEV1/FVC = Ratio forced expiratory volume in 1st second/forced vital capacity; HRCT = Chest High-resolution computer tomography of the chest; LTOT = Long-term oxygen therapy; MPA = Main pulmonary artery; NSCLC = Non-small cell lung cancer; OP = Organizing pneumonia; PFT = Pulmonary function testing; PH = Pulmonary hypertension; 2DECHO = Two-dimensional echocardiography.

INTRODUCTION

Combined Pulmonary Fibrosis with Emphysema (CPFE) is an under-recognized pulmonary syndrome characterized by the contemporaneousness of emphysema and fibrosis to varying extents within lung parenchyma. Severe dyspnea and incommensurately impaired gas exchange with embalmed lung volume are its features.¹

CASE DESCRIPTION

A 51-year-old male smoker presented with shortness of breath for 5 months, which was increased for 10 days, cough with mucoid expectoration that increased in amount for the last 10 days, no known comorbidities, no history of long-term drug intake, no pet exposure, occupation bookseller, and no significant family history.

DISCUSSION

In 2005, Cottin et al. defined a syndrome termed “combined pulmonary fibrosis and emphysema (CPFE)”, which is characterized by a history of heavy smoking, exercise-induced hypoxemia, upper lobe emphysema, lower lobe fibrosis, unanticipated near normal spirometric volumes but disproportionately severe reduction of carbon monoxide transfer.^2–4

Male gender, current or former heavy smoking, genetic susceptibility to SFTPC mutation, ABCA3 mutation, and MMP-1 Gene dysfunction are the risk factors for this syndrome.^5–7

Diagnosis of CPFE Syndrome is based on HRCT chest imaging showing the coexistence of apparent interstitial pneumonia pattern with pulmonary emphysema mixed with large thick-wall cysts.⁸

In the upper lobe, emphysema is prevailing (Fig. 1). All three major subtypes, pan-acinar, centrilobular, and paraseptal emphysema can occur in CPFE. The most common is the pan-acinar type of emphysema, as seen in our patient (Fig. 2A). The presence of paraseptal emphysema is associated with a worse prophecy.¹

In the lower lobe fibrosis is predominant, and the most common interstitial pneumonia pattern is UIP as seen in our case with diffuse basal predominant posterior subpleural peripheral irregular reticular opacities with traction bronchiectasis (Fig. 2B), honeycombing (Fig. 2C), the other being NSIP pattern with bilateral lower zone predominant ground glass opacities with or without consolidations with reticular opacities, traction bronchiectasis with subpleural sparing. The organizing pneumonia (OP) pattern is basal predominant patchy ground glassing with or without the reverse halo sign with centrilobular nodules; RB-ILD patterns are also possible. Cysts of varying size usually more than 1 cm, with thick walls of 1mm appear mostly in subpleural locations (Figs 2A and C) and can also be centrilobular in location. Fibrotic changes along the respiratory bronchioles appear as centrilobular lesions corresponding with airway-centered fibrosis.

On lung function testing, the fibrotic component fosters a restrictive pattern, that is counterbalanced by emphysematous components causing obstructive disorder in CPFE leading to a delayed diagnosis. Markedly impaired DLCO is an important clue in the diagnosis of CPFE. This is due to (A) Progressive loss of functional alveoli because of emphysema. (B) Fibrotic component leading to a decline in pulmonary capillary volume causing ventilation-perfusion discrepancy.^9,10

Respiratory tract infections, pneumothorax, heart failure, and pulmonary thromboembolism, are the causes of exacerbations in CPFE. Clinically, Acute exacerbation of CPFE is characterized by bronchospasm airflow obstruction, radiological atelectasis, mucus impaction, airway wall thickening, mediastinal lymphadenopathy, and consolidations. In case of clear signs of bacterial infection, such as if two of the three Anthonisen criteria are present antibiotics are to be added to management.^11,12

Mortality is significantly high in the patients with CPFE with a median survival of 2.1–8.5 years.¹³ Predictors of mortality in CPFE syndrome are Low BMI, clubbing, abridged FEV1, and early onset PH.¹⁴ Our patient had clubbing and also instigated moderate PH.

Pulmonary hypertension occurs early after diagnosis of CPFE and is more common in patients with emphysema-predominant CPFE, as in our patients.^15,16 High-resolution computer tomography of the chest mediastinal window (Fig. 2D) showed increased pulmonary artery to descending aorta diameter ratio indicating PH (normal ratio 1:1). The normal MPA in males is 29 mm and in females is 27 mm. His 2DECHO showed dilated RA, RV, and flattened interventricular septum causing a D-shaped ventricle (Fig. 3A), with moderate tricuspid regurgitation (Fig. 3B). A study conducted by Sir Joseph Jacob et al. concluded that PH association is more common in CPFE than in IPF cases alone without emphysema.

Combined pulmonary fibrosis with emphysema is associated with an increased risk of lung cancer. More common is non-small cell lung cancer (NSCLC) squamous cell type, compared to individual IPF or emphysema alone.¹⁷ The prognosis worsens as the patient develops lung malignancy. Due to poor lung functional reserve, the patients cannot undergo surgery, and radiotherapy may further enhance lung fibrosis.

CONCLUSION

• Combined pulmonary fibrosis with emphysema syndrome should be surmised in male smokers with sternly impaired DLCO and well-nigh preserved lung volumes. The diagnosis should be confirmed using an HRCT chest.

• Complications such as PH, increased lung cancer risk, and reiterative exacerbations are more common in CPFE, leading to a dismal prognosis.

• Hence, early diagnosis and appropriate therapy are of utmost importance to ameliorate the median survival of the infirm.

REFERENCES

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