Purpose of review: Bronchial and bronchiolar abnormalities in interstitial lung diseases (ILDs) are an issue often underestimated. However, new interstitial patterns with bronchiolar involvement are being described and the concept is still evolving. The scope of this review is to introduce a comprehensive approach to airway disorders in the context of ILDs, mainly from a pathologic perspective. Recent findings: Recent studies have revealed significant inflammatory and structural alterations at the level of small airways in idiopathic interstitial pneumonias, which may participate in the lung-remodeling pathogenetic process. A suggested pathogenetic role of cigarette smoking for lung-remodeling in smoking-related ILDs is further investigated, and unclassified fibrosis as a prominent feature in lung biopsy specimens of smokers has been established. New targeted therapies for lymphangioleiomyomatosis based on molecular and biologic properties of the disease are currently undergoing clinical trials. Combined pharmaceutical and interventional therapeutic regimens are of growing concern for refractory airway lesions in sarcoidosis. The application of volumetric high-resolution computed tomography (HRCT) chest scanning with acquisition of expiratory images provides valuable information about the involvement of small airways in ILDs. Summary: The imaging and pathologic focus on airway abnormalities in ILDs make them an integral part of their pathology with a significant pathogenetic role in interstitial processes and variable contribution to the functional status of patients.

Purpose of review: Lymphangioleiomyomatosis (LAM) is a rare but devastating disease, leading to chronic respiratory failure. Considerable progress for comprehension of the disease has been made when mutations of the tuberous sclerosis genes TSC1 and TSC2, were discovered in LAM cells. Therapeutic consequences of these studies are important, leading to clinical trials with sirolimus for LAM. Recent findings: In two studies, angiomyolipoma size decreased by 26–50% after 12 months of sirolimus treatment. In a recent 12 months controlled trial involving 89 patients with pulmonary LAM, sirolimus stopped lung function decline and improved quality of life and performance score. The protective effect of sirolimus was lost after treatment discontinuation, with a parallel lung function decline in both groups, similar to the increase in angiomyolipoma size. Sirolimus is associated with an excess of adverse events. Summary: Sirolimus represents an important drug for LAM that should be proposed to patients with a rapid alteration of lung function or with a significant clinical impairment, after individual evaluation of the risk/benefit ratio. Sirolimus seems to have a sharper effect on the reduction of abdominal masses than on lung cysts. Tolerance and safety concerns are serious limits to the long-term treatment of patients with sirolimus.

Purpose of review: Pulmonary fibrosis is a reparative response characterized by accumulation of extracellular matrix in the lung parenchyma that may be observed in end-stage sarcoidosis. This article will discuss the recent advancements in the understanding of the pathogenesis of pulmonary fibrosis in sarcoidosis in comparison with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). Recent findings: A recent study examined clinical, radiographic, and histopathologic findings of end-stage sarcoidosis patients with lung fibrosis who underwent lung transplantation. The authors found many of the patients to have moderate-to-severe interstitial pneumonitis in some cases with UIP considered to be atypical of end-stage sarcoidosis. Furthermore, these patients had diagnosis of sarcoidosis for a shorter time prior to transplant compared with individuals without interstitial pneumonitis (mean 4.8 years vs. 23.3 years). Another study found a promoter polymorphism in prostaglandin-endoperoxide synthase 2 (PTGS2), −765G>C, to be associated with susceptibility and increased risk for pulmonary fibrosis in sarcoidosis in the white population compared with healthy controls. An altered Sp1/Sp3 binding to the −765 region has been proposed as a possible mechanism for reduced PTGS2 expression. Summary: A subset of patients with sarcoidosis that progresses to pulmonary fibrosis may share some similar mechanistic and morphologic aberrations with IPF/UIP. Future studies are needed to examine the significance of chronic interstitial pneumonitits and UIP pattern in fibrotic sarcoidosis as a potential marker for progressive disease, and the roles of PTGS2 polymorphism in various ethnic groups and Sp1/Sp3 binding in other fibrotic lung diseases.

Purpose of review: There is no specific therapy for interstitial lung disease associated with connective tissue diseases (CTDs-ILD), a potentially fatal condition for some of these patients. This article reviews currently available information on the effects on CTDs-ILD of biological treatments that are increasingly used with considerable success in various systemic diseases. Recent findings: A beneficial effect of antitumor necrosis factor (TNF) agents on CTDs-ILD has been described in sporadic patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). However, and despite the fact that there was no clear evidence of pulmonary toxicity of these agents in randomized-controlled trials comprising thousands of patients with RA and spondylarthropathies, new onset or exacerbation of preexisting ILD with high mortality rates has so far been observed in 144 RA patients following anti-TNF treatment in clinical practice. Likewise, administration of the B-cell depleting anti-CD20 antibody rituximab was beneficial for ILD in SSc patients but associated with new-onset ILD in isolated patients with RA and SLE. Pertinent information on other biological treatments is currently lacking. Summary: Data on the therapeutic role of biological agents in CTDs-ILD is preliminary and controversial. Although preexisting ILD is not a contraindication for these agents, until more information is available their administration should be stopped when new pulmonary symptoms occur.