Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.

Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic P. aeruginosa infection; chronic infection due to bacteria other than P. aeruginosa. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic P. aeruginosa infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a “tree-in-bud” pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research.

Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field.

Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host–microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.

Lysosomal storage diseases (LSD) include a wide range of different disorders with variable degrees of respiratory system involvement. The purpose of this narrative review is to treat the different types of respiratory manifestations in LSD, with particular attention being paid to the main molecular pathways known so far to be involved in the pathogenesis of the disease. A literature search was conducted using the Medline/PubMed and EMBASE databases to identify studies, from 1968 through to November 2018, that investigated the respiratory manifestations and molecular pathways affected in LSD. Pulmonary involvement includes interstitial lung disease in Gaucher’s disease and Niemann-Pick disease, obstructive airway disease in Fabry disease and ventilatory disorders with chronic respiratory failure in Pompe disease due to diaphragmatic and abdominal wall muscle weakness. In mucopolysaccharidosis and mucolipidoses, respiratory symptoms usually manifest early in life and are secondary to anatomical malformations, particularly of the trachea and chest wall, and to accumulation of glycosaminoglycans in the upper and lower airways, causing, for example, obstructive sleep apnea syndrome. Although the molecular pathways involved vary, ranging from lipid to glycogen and glycosaminoglycans accumulation, some clinical manifestations and therapeutic approaches are common among diseases, suggesting that lysosomal storage and subsequent cellular toxicity are the common endpoints.

Background: Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. Case presentation: Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. Conclusions: We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as “idiopathic”. Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.