Epidemiology and management of interstitial lung disease in ANCA-associated vasculitis

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pulmonary involvement is frequently observed in AAV patients, with various possible phenotypes in the different diseases. In the last years, among the possible types of lung involvement, a growing interest has been addressed to the interstitial lung disease (ILD). Prevalence of ILD is higher in MPA than in GPA; in fact, ILD has been reported in up to 45% of MPA patients and in 23% of GPA. Anti-MPO antibodies are the main ANCA subtype associated to ILD, in about 46-71% of cases, while anti-PR3 antibodies are reported in 0-29% of patients. High resolution computed tomography (HRCT) frequently detects interstitial lung abnormalities in AAV, up to 66% of patients with MPA, even if with an unclear clinical relevance, specifically in asymptomatic patients. Ground glass opacities, mainly consistent with diffuse alveolar hemorrhage (DAH), are the most frequent finding in MPA patients, but reticulations, interlobular septal thickening and honeycombing are also reported. ILD significantly affects quality of life and survival, with mortality increased 2 to 4 times, particularly higher in MPA patients with pulmonary fibrosis. Currently, immunosuppressive therapy is considered also as a possible treatment of ILD. However, a careful evaluation of progression and severity of lung involvement, should guide the treatment decision in the single patient. In this review, we discuss the available evidence on clinical features, diagnostic work-up, prognosis and management of AAV-ILD

Influenza A/H1N1 severe pneumonia: novel morphocytological findings in bronchoalveolar lavage

We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage

Interstitial pneumonia with autoimmune features: Why rheumatologist–pulmonologist collaboration is essential

In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) “Task Force on Undifferentiated Forms of Connective Tissue Disease-associ-ated Interstitial Lung Disease” proposed classification criteria for a new research category defined as “Interstitial Pneumonia with Autoimmune Features” (IPAF), to uniformly de-fine patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment in-volvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed

Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, "real life" study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline

Noninvasive ventilation weaning in acute hypercapnic respiratory failure due to COPD exacerbation : A real-life observational study

The most recent British Thoracic Society/Intensive Care Society (BTS/ICS) guidelines on the use of noninvasive ventilation (NIV) in acute hypercapnic respiratory failure (AHRF) suggest to maximize NIV use in the first 24 hours and to perform a slow tapering. However, a limited number of studies evaluated the phase of NIV weaning. The aim of this study is to describe the NIV weaning protocol used in AHRF due to acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), patients' characteristics, clinical course, and outcomes in a real-life intermediate respiratory care unit (IRCU) setting. We performed a retrospective study on adult patients hospitalized at the IRCU of San Gerardo Hospital, Monza, Italy, from January 2015 to April 2017 with a diagnosis of AHRF due to COPD exacerbation. The NIV weaning protocol used in our institution consists of the interruption of one of the three daily NIV sessions at the time, starting from the morning session and finishing with the night session. The 51 patients who started weaning were divided into three groups: 20 (39%) patients (median age 80 yrs, 65% males) who completed the protocol and were discharged home without NIV (Completed Group), 20 (39%) did not complete it because they were adapted to domiciliary ventilation (Chronic NIV Group), and 11 (22%) interrupted weaning ex abrupto mainly due to NIV intolerance (Failed Group). Completed Group patients were older, had a higher burden of comorbidities, but a lower severity of COPD compared to Chronic NIV Group. Failed Group patients experienced higher frequency of delirium after NIV discontinuation. None of the patients who completed weaning had AHRF relapse during hospitalization. While other NIV weaning methods have been previously described, our study is the first to describe a protocol that implies the interruption of a ventilation session at the time. The application of a weaning protocol may prevent AHRF relapse in the early stages of NIV interruption and in elderly frail patients

Interstitial lung disease and anti-myeloperoxidase antibodies: Not a simple association

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7–23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients’ survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease

Differences between acute exacerbations of idiopathic pulmonary fibrosis and other interstitial lung diseases.

Interstitial lung diseases (ILDs) comprise a wide group of pulmonary parenchymal disorders. These patients may experience acute respiratory deteriorations of their respiratory condition, termed “acute exacerbation” (AE). Incidence of AE-ILD seems to be lower than idiopathic pulmonary fibrosis (IPF), but prognosis and prognostic factors are largely unrecognized. We retrospectively analyzed a cohort of 158 consecutive adult patients hospitalized for AE-ILD in two Italian University hospitals from 2009 to 2016. Patients included in the analysis has been divided into two groups: non-IPF (62%) and IPF (38%). Among ILDs included in the non-IPF group, the most frequent diagnoses were non-specific interstitial pneumonia (NSIP) (42%) and connective tissue disease (CTD)-ILD (20%). Mortality during hospitalization was significantly different between the two groups, respectively 19% in non-IPF group and 43% in IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers with neutrophilia on differential blood cell count (HR 1.02 [CI 1.01 – 1.04]), presence of pulmonary hypertension (HR 1.85 – [CI 1.17 – 2.92]) and diagnosis of IPF (HR 2.31 [CI 1.55 – 3.46]) resulted negative prognostic factors in our analysis, while lymphocytosis on differential count seemed to act as a protective prognostic factor (OR 0.938 [CI 0.884 – 0.995]). Further prospective, large-scale, real-world data are needed to support and confirm the impact of our findings

Serum and exhaled breath condensate inflammatory cytokines in community-acquired pneumonia: a prospective cohort study

Background The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation. Methods This was an observational, prospective, cohort study of hospitalised patients with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin [IL]-1, IL-1\u3b1, IL-1\u3b2, IL-2, IL-6, IL-8, tumor necrosis factor [TNF]\u3b1 and interferon [IFN]\u3b3) and anti-inflammatory cytokines (IL-4 and IL-10) were measured in both serum and exhaled breath condensate within 24 h after hospital admission. Results A total of 74 patients (median age: 76 years; gender: 61 % male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in patients with severe disease on admission and prolonged time to reach clinical stability. This was due to lower levels of anti-inflammatory cytokines in the exhaled breath condensate and higher levels of pro-inflammatory cytokines in serum. Conclusions Dis-regulation between pro- and anti-inflammatory pathways might be a part of the pathogenic mechanisms that lead to severe infection and worse early clinical outcomes in CAP patients

Phenotyping in bronchiectasis: are we moving toward a personalized medicine?

Bronchiectasis (BE) is a heterogeneous disease. Similarly, to other chronic airway diseases, such as asthma and chronic obstructive pulmonary disease, management of BE patients requires a specific and personalized treatment that depends on many clinical, functional, and microbiological variables. Therefore, developing phenotyping methods that can help clinical and therapeutic choices is of paramount importance. Various methodological approaches have been used to personalize patients' management. In this review, we explore the main tools identified so far to classify and phenotype BE patients, including the approaches based on BE etiologies, disease severity, cluster analysis, and endotyping. We also discuss the strengths and limitations of every approach and highlight the similarities and differences between these studies. Finally, we review the therapeutic implications and clinical management connected with each approach

Covid-19 and the role of smoking: The protocol of the multicentric prospective study COSMO-IT (covid19 and smoking in italy)

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality