Owing to the offsetting influences of emphysema and pulmonary fibrosis, CPFE may be present despite near-normal spirometry in patients with parenchymal lung disease. This presents something of a diagnostic conundrum, as changes in pulmonary compliance are counterbalanced by each condition. Emphysema is characterized by loss of elasticity, with poor air flow, air trapping, and hyperinflation. Conversely, while fibrotic lung diseases demonstrate more efficient air emptying than emphysema, the patient’s lung capacity and volume are reduced. The result is pseudonormalization of spirometry parameters; therefore, the forced expiratory volume in 1 second and the forced vital capacity may be normal or near normal. Nonetheless, the patient is quite dyspneic and generally hypoxemic. If you are relying on the spirometry results, you may be puzzled as to why the patient is so impaired. A more complete set of pulmonary function tests, together with a high-resolution computed tomography (HRCT), will clarify that, despite the unimpressive spirometry results, the diffusing capacity for carbon monoxide is markedly reduced. The combination of centrilobular emphysema and fibrosis on HRCT further elucidates this and should guide the clinician to the correct diagnosis (ie, CPFE).

After establishing the diagnosis of CPFE, patients are typically followed symptomatically and/or periodically with pulmonary function tests and HRCT imaging. There is little justification to date, however, for more extensive testing in patients who are stable from the perspective of symptoms and oxygenation. Many patients gradually demonstrate acute or subacute deterioration in symptoms or oxygenation. Infection, ischemic heart disease, myocardial infarction, and congestive heart failure are all known contributing factors to acute deterioration in CPFE, which typically unfolds over a period of a few days or weeks. With respect to subacute deterioration, evidence suggests that untreated gastroesophageal reflux disease may play a role. Other factors include exposure to toxic drugs or other inhaled substances that can precipitate fibrotic changes (eg, exposure to cigarette smoke, birds, hot tub chemicals, organic and inorganic dust), most of which can be effectively addressed by avoidance.

Patients with CPFE are particularly at increased risk for group 3 pulmonary hypertension, presenting as elevated pulmonary arterial pressures, associated increased right ventricular afterload, right ventricular enlargement, and right ventricular systolic hypocontractility. Clinicians should be alert to the fact that cor pulmonale may explain either an acute or subacute decline, depending on the rapidity of right ventricular decompensation and precipitating circumstances. For example, atrial fibrillation may be poorly tolerated or dietary indiscretion with increased sodium and fluid intake may lead to worsening right heart dysfunction. The prevalence of group 3 pulmonary hypertension in idiopathic pulmonary fibrosis ranges widely in the published literature; however, a significant proportion have severe pulmonary hypertension and worse survival. Chronic respiratory failure with both resting and exertional hypoxemia is more frequent in CPFE compared with patients with pure emphysema or pure fibrosis, resulting in a poorer prognosis. There are many other factors that may lead to deterioration.  Of note, patients with CPFE also have an increased risk of developing lung cancer. The presence of hemoptysis or pleural effusion may lead to the discovery of bronchogenic carcinoma and should raise suspicion for cancer as the potential explanation for either an acute or subacute deterioration in the patient’s condition. Obstructive sleep apnea is another commonly associated condition that should be considered, particularly if the body habitus is suggestive or if there is upper airway narrowing on physical examination.