Systemic Corticosteroids for Treating Respiratory Diseases: Less Is Better, but When and How Is It Possible in Real Life?

Systemic corticosteroids (CSs), a keystone in pulmonology, are drugs with strong antiinflammatory activity. They are cheap, easily available, and accessible, but with common and serious side effects. Moreover, the use of exogenous CSs may suppress the hypothalamic-pituitary-adrenal (HPA) axis, predisposing to adrenal insufficiency. Safe CS treatment is a challenge of pharmacological research. This narrative review examined the indications of CSs in some respiratory diseases, analyzing what types, dosages, and length of treatment are required as the dosage and duration of CS treatments need to be minimized. Chronic maintenance treatments with CSs are associated with poor prognosis, but they are still prescribed in patients with severe asthma, Chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. When CS discontinuation is not possible, all efforts should be made to achieve clinically meaningful reductions. Guidelines suggest the use of methylprednisolone at a dose of 20-40 mg/day or equivalent for up to 10 days in subjects with COVID-19 pneumonia (but not other respiratory viral diseases) and respiratory failure, exacerbations of asthma, and COPD. Some guidelines suggest that CS treatment shorter than 10-14 days can be abruptly stopped, strictly monitoring subjects with unexplained symptoms after CS withdrawal, who should promptly be tested for adrenal insufficiency (AI) and eventually treated. CSs are often used in severe community-acquired pneumonia associated with markedly increased serum inflammation markers, in acute respiratory distress syndrome (ARDS), in septic shock unresponsive to hydro-saline replenishment and vasopressors, and acute exacerbations of interstitial lung diseases. As these cases often require higher doses and longer duration of CS treatment, CS tapering should be gradual and, when useful, supported by an evaluation of HPA axis function.

The Effects of Interstitial Lung Diseases on Alveolar Extracellular Vesicles Profile: A Multicenter Study.

Diagnosis of interstitial lung diseases (ILD) is difficult to perform. Extracellular vesicles (EVs) facilitate cell-to-cell communication, and they are released by a variety of cells. Our goal aimed to investigate EV markers in bronchoalveolar lavage (BAL) from idiopathic pulmonary fibrosis (IPF), sarcoidosis and hypersensitivity pneumonitis (HP) cohorts. ILD patients followed at Siena, Barcelona and Foggia University Hospitals were enrolled. BAL supernatants were used to isolate the EVs. They were characterized by flow cytometry assay through MACSPlex Exsome KIT. The majority of alveolar EV markers were related to the fibrotic damage. CD56, CD105, CD142, CD31 and CD49e were exclusively expressed by alveolar samples from IPF patients, while HP showed only CD86 and CD24. Some EV markers were common between HP and sarcoidosis (CD11c, CD1c, CD209, CD4, CD40, CD44, CD8). Principal component analysis distinguished the three groups based on EV markers with total variance of 60.08%. This study has demonstrated the validity of the flow cytometric method to phenotype and characterize EV surface markers in BAL samples. The two granulomatous diseases, sarcoidosis and HP, cohorts shared alveolar EV markers not revealed in IPF patients. Our findings demonstrated the viability of the alveolar compartment allowing identification of lung-specific markers for IPF and HP.

BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures.

Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown etiology. Although antifibrotic treatments have shown a reduction of lung function decline and a slow disease progression, IPF is characterize by a very high mortality. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, besides sharing similar pathogenic pathways. Lung cancer (LC) diagnosis is often difficult in IPF patients because of the diffuse lung injuries and abnormalities due to the underlying fibrosis. This is reflected in the lack of optimal therapeutic strategies for patients with both diseases. For this purpose, we performed a proteomic study on bronchoalveolar lavage fluid (BALF) samples from IPF, LC associated with IPF (LC-IPF) patients, and healthy controls (CTRL). Molecular pathways involved in inflammation, immune response, lipid metabolism, and cell adhesion were found for the dysregulated proteins in LC-IPF, such as TTHY, APOA1, S10A9, RET4, GDIR1, and PROF1. The correlation test revealed a relationship between inflammation- and lipid metabolism-related proteins. PROF1 and S10A9, related to inflammation, were up-regulated in LC-IPF BAL and serum, while APOA1 and APOE linked to lipid metabolism, were highly abundant in IPF BAL and low abundant in IPF serum. Given the properties of cytokine/adipokine of the nicotinamide phosphoribosyltransferase, we also evaluated its serum abundance, highlighting its down-regulation in LC-IPF. Our retrospective analyses of BAL samples extrapolated some potential biomarkers of LC-IPF useful to improve the management of these contemporary pathologies. Their differential abundance in serum samples permits the measurement of these potential biomarkers with a less invasive procedure.

Combined Sarcoidosis and Idiopathic Pulmonary Fibrosis (CSIPF): A New Phenotype or a Fortuitous Overlap? Scoping Review and Case Series.

Idiopathic pulmonary fibrosis (IPF) and sarcoidosis are two distinct clinical entities with different aetiology, epidemiology, risk factors, symptoms and chest imaging. A number of papers have reported an overlap of the two diseases and have suggested the existence of a distinct phenotype defined as combined sarcoidosis and idiopathic pulmonary fibrosis (CSIPF). We used the scoping review protocol to review the literature on CSIPF. We also enrolled a cohort of nine CSIPF patients and compared them with lone-IPF and fibrotic sarcoidosis patients. Our CSIPF cohort showed male prevalence and only ex-smokers. Functional assessment at baseline showed mild to moderate restrictive impairment of lung volumes in lone-IPF and CSIPF patients, associated with moderate-to-severe reduction in DLco percentages. Although all CSIPF patients were on antifibrotic treatments, functional impairment occurred in the two years of follow up. This suggests the importance of considering these patients at high risk of rapid deterioration and lung damage.