Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows.

Pirfenidone and Nintedanib are specific drugs used against idiopathic pulmonary fibrosis (IPF) that showed efficacy in non-IPF fibrosing interstitial lung diseases (ILD). Both drugs have side effects that affect patients in different ways and have different levels of severity, making treatment even more challenging for patients and clinicians. The present review aims to assess the effectiveness and potential complications of Pirfenidone and Nintedanib treatment regimens across various ILD diseases. A detailed search was performed in relevant articles published between 2018 and 2023 listed in PubMed, UpToDate, Google Scholar, and ResearchGate, supplemented with manual research. The following keywords were searched in the databases in all possible combinations: Nintedanib; Pirfenidone, interstitial lung disease, and idiopathic pulmonary fibrosis. The most widely accepted method for evaluating the progression of ILD is through the decline in forced vital capacity (FVC), as determined by respiratory function tests. Specifically, a decrease in FVC over a 6-12-month period correlates directly with increased mortality rates. Antifibrotic drugs Pirfenidone and Nintedanib have been extensively validated; however, some patients reported several side effects, predominantly gastrointestinal symptoms (such as diarrhea, dyspepsia, and vomiting), as well as photosensitivity and skin rashes, particularly associated with Pirfenidone. In cases where the side effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. However, further research is needed to optimize the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. Finally, other studies are requested to establish the treatments that can stop ILD progression.

Vascular Endothelial Damage in COPD: Where Are We Now, Where Will We Go?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has higher rates among the general population, so early identification and prevention is the goal. The mechanisms of COPD development have not been completely established, although it has been demonstrated that endothelial dysfunction plays an important role. However, to date, the measurement of endothelial dysfunction is still invasive or not fully established. Nailfold video capillaroscopy (NVC) is a safe, non-invasive diagnostic tool that can be used to easily evaluate the microcirculation and can show any possible endothelial dysfunctions early on. The aim of this review is to evaluate if nailfold microcirculation abnormalities can reflect altered pulmonary vasculature and can predict the risk of cardiovascular comorbidities in COPD patients. METHODS: A systematic literature search concerning COPD was performed in electronic databases (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until March 2024. The following search words were searched in the databases in all possible combinations: chronic obstructive pulmonary disease (COPD), endothelial damage, vascular impairment, functional evaluation, capillaroscopy, video capillaroscopy, nailfold video capillaroscopy. Only manuscripts written in English were considered for this review. Papers were included only if they were able to define a relationship between COPD and endothelium dysfunction. RESULTS: The search selected 10 articles, and among these, only three previous reviews were available. Retinal vessel imaging, flow-mediated dilation (FMD), and skin autofluorescence (AF) are reported as the most valuable methods for assessing endothelial dysfunction in COPD patients. CONCLUSIONS: It has been assumed that decreased nitric oxide (NO) levels leads to microvascular damage in COPD patients. This finding allows us to assume NVC's potential effectiveness in COPD patients. However, this potential link is based on assumption; further investigations are needed to confirm this hypothesis.

Nailfold Capillaroscopy Analysis Can Add a New Perspective to Biomarker Research in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), all of which are characterised by inflammation of small-medium-sized vessels. Progressive understanding of these diseases has allowed researchers and clinicians to start discussing nailfold video capillaroscopy (NVC) as a future tool for many applications in daily practice. Today, NVC plays a well-established and validated role in differentiating primary from secondary Raynaud's phenomenon correlated with scleroderma. Nevertheless, there has not been sufficient attention paid to its real potential in the ANCA-associated vasculitis. In fact, the role of NVC in vasculitis has never been defined and studied in a multicentre and multinational study. In this review, we carried out a literature analysis to identify and synthesise the possible role of capillaroscopy for patients with ANCA-associated vasculitis. METHODS: Critical research was performed in the electronic archive (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until November 2023. The following search words were searched in the databases in all possible combinations: capillaroscopy, video capillaroscopy, nailfold-video capillaroscopy, ANCA-associated vasculitis, vasculitis, granulomatosis with polyangiitis, EGPA, and microscopic polyangiitis. RESULTS: The search identified 102 unique search results. After the evaluation, eight articles were selected for further study. The literature reported that capillaroscopy investigations documented non-specific abnormalities in 70-80% of AAV patients. Several patients showed neoangiogenesis, capillary loss, microhaemorrhages, and bushy and enlarged capillaries as the most frequent findings. Furthermore, the difference between active phase and non-active phase in AAV patients was clearly discernible. The non-active phase showed similar rates of capillaroscopy alterations compared to the healthy subjects, but the active phase had higher rates in almost all common abnormalities instead. CONCLUSIONS: Microvascular nailfold changes, observed in patients affected by vasculitis, may correlate with the outcome of these patients. However, these non-specific abnormalities may help in the diagnosis of vasculitis. As such, new analysis analyses are necessary to confirm our results.