Mediat. Inflamm.

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL perpendicular to 1116 versus 59 perpendicular to 25; P < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation

Hypersensitivity pneumonitis: an overlooked cause of cough and dyspnea.

Hypersensitivity pneumonitis (HP) is an immune-mediated pulmonary disorder involving inflammation of the lung interstitium, terminal bronchioles, and alveoli caused by the immune response to the inhalation of an offending environmental airborne agent. It can manifest as exertional dyspnea, fatigue, weight loss, and progressive respiratory failure if left untreated. Because of its protean features, it can be misdiagnosed as other common obstructive lung conditions such as asthma. If triggers are not avoided, it can progress to irreversible pulmonary fibrosis. In this article, we present the case of a 51-year-old male who presented to our hospital with recurrent bouts of dyspnea and cough, initially diagnosed as an asthma exacerbation. He received a final diagnosis of HP after investigation of his workplace revealed airborne spores and surface molds from multiple fungal species, serology revealed eosinophilia, and computed tomography showed bronchiectasis. Avoidance of occupational exposure resulted in significant improvement of his respiratory symptoms after two months

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p