Editorials

The Syndrome of Combined Pulmonary Fibrosis and Emphysema

The syndrome of combined pulmonary fibrosis and emphysema (CPFE) primarily due to tobacco smoking has been reported in connective tissue disease, but little is known about its characteristics in systemic sclerosis (SSc).

In this retrospective multi-center case-control study, we identified 36 SSc patients with CPFE, and compared them with 72 SSc controls with interstitial lung disease (ILD) without emphysema.

Rate of CPFE in SSc patients with CT scan was 3.6%, and 7.6% among SSc patients with ILD. CPFE-SSc patients were more likely to be male (75 % vs 18%, p < 0.0001), smokers (83 % vs 33%, p < 0.0001), and to have limited cutaneous SSc (53 % vs 24% p < 0.01) than ILD-SSc controls. No specific autoantibody was significantly associated with CPFE. At diagnosis, CPFE-SSc patients had a greater decrease in carbon monoxide diffusing capacity (DLCO 39 ± 13 % vs 51 ± 12% of predicted value, p < 0.0001) when compared to SSc-ILD controls, whereas lung volumes (total lung capacity and forced vital capacity) were similar. During follow-up, CPFE-SSc patients more frequently developed precapillary pulmonary hypertension (PH) (44 % vs 11%, p < 10⁻⁴), experienced more frequent unscheduled hospitalizations (50 % vs 25%, p < 0.01), and had decreased survival (p < 0.02 by Kaplan–Meier survival analysis) as compared to ILD-SSc controls.

The CPFE syndrome is a distinct pulmonary manifestation in SSc, with higher morbidity and mortality. Early diagnosis of CPFE by chest CT in SSc patients (especially smokers) may result in earlier smoking cessation, screening for PH, and appropriate management.

Idiopathic Pulmonary Fibrosis (IPF) and Sarcoidosis are distinct clinical entities. Fibrotic disease in pulmonary sarcoidosis is typically upper lobe predominant. In IPF fibrosis is basilar and peripheral predominant [usual interstitial pneumonia (UIP) pattern]. Sarcoidosis and UIP have rarely been observed in the same patient. We sought to characterize patients manifesting both sarcoidosis and IPF and compare clinical features and survival to that of patients with “Lone-IPF” (IPF only) and pulmonary sarcoidosis with fibrosis in a non-UIP pattern.

Patients were identified from a clinical database and data abstracted from medical records (1995–2016): 1) 25 patients with combined sarcoidosis and IPF (CSIPF) defined by clinical and histological features of sarcoidosis and HRCT features of possible or definite UIP or UIP by histopathology; 2) Randomly selected control patients during the same period: 28 Lone-IPF, 25 stage III/IV pulmonary sarcoidosis.

The gender and race of patients with CSIPF and Lone-IPF patients were similar (68% male and 84% Caucasian), as were survival outcomes. Mean time from IPF diagnosis to death: 3.2 years CSIPF, 3.6 years Lone-IPF (log rank p value 0.49). Among patients with pulmonary sarcoidosis, mean time from diagnosis to death: 21.4 years.

Clinical characteristics/behavior of patients with CSIPF was similar to Lone-IPF patients. It is possible that patients with sarcoidosis coincidentally developed IPF and/or have occult genetic predisposition factors to manifest both diseases at different time points. Further study is needed.

Chronic obstructive pulmonary disease (COPD) is commonly associated with other chronic diseases, which poses several diagnostic and therapeutic problems. Indeed, important comorbidities frequently remain unrecognized and, then, untreated, whereas respiratory drugs may have non respiratory side effects, and selected non respiratory drugs may variably affect the respiratory function.

to describe: how COPD affects the presentation and contributes to the diagnostic challenges of its most common comorbidities; how coexisting COPD impacts the therapeutic approach to selected comorbidities and viceversa.

we distinguish comorbidities of COPD depending upon whether they are complications of COPD or share risk factors, mainly smoke, with it or, finally, aggravate COPD. We describe atypical presentations of and diagnostic clues to comorbidities and suggest screening procedures. Finally, the main therapeutic problems, as resulting from the risk of untoward effects of therapies of COPD and its comorbidity, with special attention to drug-drug interactions and possible overdosages, are described.

selected complications of COPD, such as osteoporosis, sarcopenia and dysphagia, are rarely recognized and treated, likely due to the poor awareness of them. Important comorbidities, such as coronary artery disease, chronic heart failure, obstructive sleep apnoea syndrome and chronic renal failure, also should be systematically searched for because of their commonly variant presentation. Disease-related symptoms should be distinguished from drug effects or drug-drug interaction effects.

a truly comprehensive view of the complex COPD patient, hopefully capitalizing on multidimensional geriatric assessment, is needed to dissect the many components of health status impairment and to provide the optimal care. Selected screening procedures are highly desirable to identify frequently missed comorbidities. Pharmacosurveillance is an essential part of the approach to COPD and its comorbidities.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown etiopathogenesis with limited therapeutic options. IPF is characterized by an abundance of fibroblasts and loss of epithelial progenitors, which cumulates in unrelenting fibrotic lung remodeling and loss of normal oxygenation. IPF has been challenging to model in rodents; nonetheless, mouse models of lung fibrosis provide clues as to the natural progression of lung injury and remodeling, but many have not been useful in predicting efficacy of therapeutics in clinical IPF. We provide a detailed methodologic description of various iterations of humanized mouse models, initiated by the i.v. injection of cells from IPF lung biopsy or explants specimens into severe combined immunodeficiency (SCID)/beige or nonobese diabetic SCID γ mice. Unlike cells from normal lung samples, IPF cells promote persistent, nonresolving lung remodeling in SCID mice. Finally, we provide examples and discuss potential advantages and pitfalls of human-specific targeting approaches in a humanized SCID model of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and ultimately fatal disease of the lung with an unknown etiology and few treatment options. Recognition of patients who fall into phenotypic subsets may provide earlier opportunities for initiation of therapy or referral to transplant. In addition, identification and management of comorbidities may improve quality of life, and this may be more important to some patients than extending survival. This chapter updates prior summaries of proposed phenotypes and comorbidities in IPF (Fell, 2012).