Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience

Pirfenidone and nintedanib are the only two drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF). Both proved to be safe and well-tolerated in clinical trials, but real-world data and direct comparisons are scarce. This real-life study explored the safety profile of pirfenidone and nintedanib with a prolonged follow-up. We retrospectively collected clinical status, adverse events (AEs), and treatment changes from IPF patients who had started an antifibrotic treatment at our centre from December 2011 to December 2020, including 192 patients treated with pirfenidone and 89 with nintedanib. The majority of patients in both groups experienced one or more AEs during the follow-up. A higher proportion of AEs in the nintedanib group were effectively treated with behavioural modifications or additional medications compared with the pirfenidone group (52.5% vs. 40.6%, p = 0.04). Overall, a difference in the impact of AEs due to nintedanib versus pirfenidone resulted in a lower permanent discontinuation of therapy (8.3% vs. 18.3%, p = 0.02), with the latter being associated with a higher risk of drug discontinuation at 48 months after initiation (OR = 2.52, p = 0.03). Our study confirms the safety profile of antifibrotic drugs in IPF but highlights that AEs due to nintedanib are usually easier to manage and lead to fewer cases of permanent discontinuation of therapy

Which Therapy for Non-Type(T)2/T2-Low Asthma

Currently, the asthmatic population is divided into Type 2-high and non-Type 2/Type 2-low asthmatics, with 50% of patients belonging to one of the two groups. Differently from T2-high, T2-low asthma has not been clearly defined yet, and the T2-low patients are identified on the basis of the absence or non-predominant expression of T2-high biomarkers. The information about the molecular mechanisms underpinning T2-low asthma is scarce, but researchers have recognized as T2-low endotypes type 1 and type 3 immune response, and remodeling events occurring without inflammatory processes. In addition, the lack of agreed biomarkers reprents a challenge for the research of an effective therapy. The first-choice medication is represented by inhaled corticosteroids despite a low efficacy is reported for/in T2-low patients. However, macrolides and long-acting anti-muscarinic drugs have been recognized as efficacious. In recent years, clinical trials targeting biomarkers playing key roles in T3 and T1 immune pathways, alarmins, and molecules involved in neutrophil recruitment have provided conflicting results probably misleading (or biased) in patients’ selection. However, further studies are warranted to achieve a precise characterization of T2-low asthma with the aim of defining a tailored therapy for each single asthmatic patient

Nitric oxide's physiologic effects and potential as a therapeutic agent against COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for COVID-19 pneumonia, a pandemic that precipitates huge pressures on the world's social and economic systems. Disease severity varies among individuals. SARS-CoV-2 infection can be associated with e.g. flu-like symptoms, dyspnoea, severe interstitial pneumonia, acute respiratory distress syndrome, multiorgan dysfunction, and generalized coagulopathy. Nitric oxide (NO), is a small signal molecule that impacts pleiotropic functions in human physiology, which can be involved in the significant effects of COVID-19 infection. NO is a neurotransmitter involved in the neural olfactory processes in the central nervous system, and some infected patients have reported anosmia as a symptom. Additionally, NO is a well-known vasodilator, important coagulation mediator, anti-microbial effector and inhibitor of SARS-CoV replication. Exhaled NO is strongly related to the type-2 inflammatory response found in asthma, which has been suggested to be protective against SARS-CoV-2 infection. Several reports indicate that the use of inhaled NO has been an effective therapy during this pandemic since the ventilation-perfusion ratio in COVID-19 patients improved afterwards and they did not require mechanical ventilation. The aim of this mini-review is to summarize relevant actions of NO that could be beneficial in the treatment of COVID-19