Combined Pulmonary Fibrosis and Emphysema in Scleroderma-Related Lung Disease Has a Major Confounding Effect on Lung Physiology and Screening for Pulmonary Hypertension.

OBJECTIVE: To assess the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD) and the effect of CPFE on the pulmonary function tests used to evaluate the severity of SSc-related ILD and the likelihood of pulmonary hypertension (PH). METHODS: High-resolution computed tomography (HRCT) scans were obtained in 333 patients with SSc-related ILD and were evaluated for the presence of emphysema and the extent of ILD. The effects of emphysema on the associations between pulmonary function variables and the extent of SSc-related ILD as visualized on HRCT and echocardiographic evidence of PH were quantified. RESULTS: Emphysema was present in 41 (12.3%) of the 333 patients with SSc-related ILD, in 26 (19.7%) of 132 smokers, and in 15 (7.5%) of 201 lifelong nonsmokers. When the extent of fibrosis was taken into account, emphysema was associated with significant additional differences from the expected values for diffusing capacity for carbon monoxide (DLco) (average reduction of 24.1%; P < 0.0005), and the forced vital capacity (FVC)/DLco ratio (average increase of 34.8%; P < 0.0005) but not FVC. These effects were identical in smokers and nonsmokers. Multivariate analysis showed that the presence of emphysema had a greater effect than echocardiographically determined PH on the FVC/DLco ratio, regardless of whether it was analyzed as a continuous variable or using a threshold value of 1.6 or 2.0. CONCLUSION: Among patients with SSc-related ILD, emphysema is sporadically present in nonsmokers and is associated with a low pack-year history in smokers. The confounding effect of CPFE on measures of gas exchange has major implications for the construction of screening algorithms for PH in patients with SSc-related ILD.

Differential telomerase expression in idiopathic pulmonary fibrosis and non-small cell lung cancer.

Telomerase is a reverse transcriptase ribonucleo-protein (h-TERT) that synthesizes telomeric repeats using its RNA component (h-TERC) as a template. Telomerase dysfunction has been associated with both fibrogenesis and carcinogenesis. In this study, we aimed to evaluate the telomerase mRNA expression levels of both subunits (h-TERT and h-TERC) in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC), since there are indications of common pathogenetic pathways in these diseases. We prospectively examined lung tissue samples from 29 patients with IPF, 10 patients with NSCLC and 21 controls. Furthermore, we examined BALF samples from 31 patients with NSCLC, 23 patients with IPF and 12 control subjects. The mRNA expression for both h-TERT and h-TERC was measured by real-time RT-PCR. In the lung tissue samples, both h-TERT and h-TERC mRNA expression levels varied among the 3 groups (p=0.036 and p=0.002, respectively). h-TERT mRNA levels in the patients with IPF were lower compared with those in the controls (p=0.009) and patients with NSCLC (p=0.004). h-TERC mRNA levels in the patients with IPF were lower compared with those in the controls (p=0.0005) and patients with NSCLC (p=0.0004). In the BALF samples, h-TERT mRNA expression levels varied among the groups (p=0.012). More specifically, h-TERT mRNA levels in the patients with IPF were higher compared with those in the controls (p=0.03) and patients with NSCLC (p=0.007). The attenuation of telomerase gene expression in IPF in comparison to lung cancer suggests a differential role of this regulatory gene in fibrogenesis and carcinogenesis. Further functional studies are required in order to further elucidate the role of telomerase in these devastating diseases.

An update on idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic disease with a median survival of 3-5 years. Despite recent advances the pathophysiology of the disease remains not fully understood. However, injury of type II alveolar epithelial cells is considered the key event for the initiation of the development of fibrosis. An accurate diagnosis is imperative because commencing treatment at an early stage may reduce disease progression. In this regard, the multidisciplinary disease meeting between pulmonologists, radiologists and pathologists has definitely improved the diagnostic confidence. Importantly, a milestone has been recently reached as the first IPF-specific drug namely pirfenidone has been licensed in Europe, Japan and Asia.

Recent advances in the pathogenesis and clinical evaluation of pulmonary fibrosis.

Interstitial lung diseases (ILDs) are a group of heterogeneous disorders, either idiopathic or associated with injurious or inflammatory causes, in which the major site of damage is the lung interstitium. For a long time, knowledge regarding pathogenesis was trivial and there were difficulties in diagnosing and subsequently treating these diseases. During the past decade, however, there has been an impressive development in the field of ILDs. Idiopathic pulmonary fibrosis, the most common and fatal form of ILD, was initially believed to be due to an inflammatory response to unknown lung injury, whereas nowadays it is believed to be the result of multiple injuries at different sites of the lung followed by aberrant repair. The integration of clinical, radiological and histological data, namely a multidisciplinary team (MDT) approach, has provided grounds for a more accurate diagnosis of ILDs, and helped the identification of different entities and development of different therapeutic approaches. However, because of the complexity of ILDs, even this approach may fail to establish a confident diagnosis. How should the clinician behave in this case and what are the pitfalls of the MDT approach? In addition, since diagnosis is the major predictor of prognosis, are there any other tools available to predict prognosis?

Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement.

The connective tissue disorders (CTDs), also called collagen vascular diseases (CVDs), represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs. Individuals with a CTD (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, polymyositis/dermatomyositis and mixed connective tissue disease) are susceptible to respiratory involvement. When the lungs are affected, an increasing mortality and morbidity in CVDs occurs. Interstitial lung disease (ILD) is established as a clinical corollary across the spectrum of CTDs, with an overall incidence estimated at 15%. Therefore, pivotal clinical dilemmas remain in the evaluation and management of ILD involvement in CVDs. Critical questions are the presence of fibrosis and whether the disease is clinically significant. Moreover, the clinician has to decide if treatment is warranted and which is the best therapeutic approach. The use of additional tests, such as pulmonary function tests, high-resolution computed tomography scan, bronchoalveolar lavage fluid and surgical lung biopsy, deserves better discussion. The present review focuses on establishing the diagnosis of ILD in CTD, and on evaluating disease activity and prognosis. This will provide the basis for therapeutic decisions that will be discussed, including an overview of recent advances.