We here report the first case of anti-proteinase 3-positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver involvement and alveolar haemorrhage. Two weeks after vaccination, a 49-year-old man developed inflammatory arthralgias and hypertransaminasaemia. Two months later, fever and haemoptysis appeared; the patient tested positive for anti-proteinase 3 autoantibodies. High-dose steroids and rituximab were started, and complete remission was achieved. Systemic autoimmune diseases, including ANCA-associated vasculitis, should always be considered in the differential diagnosis of hypertransaminasaemia, especially when the clinical context is suspicious.

Aim: The aim of our study is to compare respiratory function, physical performance and nutritional parameters at the time of disease diagnosis and after 6 months of follow-up in a cohort of patients with IPF followed-up prospectively in 9 IPF referral centers in northern Italy. Methods: The study consisted of two respiratory assessment and two nutritional evaluations at baseline and 6-month follow-up. Results: 90 patients were included in the study, however only 82 patients with both pneumological assessments were included in this analysis. In regards to PFTs and DLCO did not significantly change between baseline and 6 months follow-up. Similarly, no differences were observed in the 4-meter gait speed test, distance walked at 6MWT and hand-grip strength. Mean BMI significantly decreased (p<0.001) as significantly increased the proportion of patients who lost more than 5% of weight in the prior 6 months (p=0.004). Anthropometric measurements, arm and abdominal circumference significantly decreased between baseline and follow-up. These changes in the nutritional status also led to a modification in the nutritional phenotypes with a reduction in the proportion of obese and normonourished patients and an increase in patients with sarcopenia (Figure 1). Conclusions: We did not observe a significant change in pulmonary function and physical performance parameters iduring the 6-month follow-up. However, worsening of multiple nutritional parameters was detected, including loss of weight, reduction of both body fat and lean mass at BIA. These nutritional changes were reflected in a reduction of patients who showed an obese or normonourished phenotype and increasing in the proportion of sarcopenic patients.

Background Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. Aim Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. Methods Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. Results Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. Conclusions The prevalence of sarcopenia in patients with IPF both at diagnosis and at 6-month follow-up was low but not negligible and was associated with higher severity of the disease and sedentary lifestyle. In IPF patients, a comprehensive diagnostic work-up including all the criteria defining the EWGSOP2 definition might be more useful than a series testing for prompt recognition of nutritional and physical performance abnormalities.

Background Nutritional status impacts quality of life and prognosis of patients with respiratory diseases, including idiopathic pulmonary fibrosis (IPF). However, there is a lack of studies performing an extensive nutritional assessment of IPF patients. This study aimed to investigate the nutritional status and to identify nutritional phenotypes in a cohort of IPF patients at diagnosis. Methods Patients underwent a thorough pulmonary and nutritional evaluation including questionnaires on nutritional status, and physical activity, anthropometry, body impedance, dynamometry, 4-m gait speed and blood tests. Results 90 IPF patients (78.9% males, mean age 72.7 years) were enrolled. The majority of patients were classified as Gender-Age-Physiology Index stage 2 (47, 52.2%) with an inactive lifestyle according to International Physical Activity Questionnaire score (39, 43.3%), and had mean forced vital capacity and diffusing capacity for carbon monoxide 86.5% and 54.2%, respectively. In regards to nutritional phenotypes, the majority of patients were normally nourished (67.8%, 95% CI 58.6–77.7%), followed by non-sarcopenic obese (25.3%, 95% CI 16.1–35.2%), sarcopenic (4.6%, 95% CI 0.0–14.5%) and sarcopenic obese (2.3%, 95% CI 0.0–12.2%). Among the normally nourished, 49.2% showed early signs of nutritional and physical performance alterations, including body mass index ≥30 kg·m −2 in 4.3%, history of weight loss ≥5% in 11.9%, and reduction of gait speed and hand grip strength in 11.9% and 35.6%, respectively. Low vitamin D values were observed in 56.3% of cases. Conclusions IPF patients at diagnosis are mainly normally nourished and obese, but early signs of nutritional and physical performance impairment can already be identified at this stage.

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.

Introduction: Nutritional status (NS) impacts quality of life and prognosis of patients with respiratory diseases. The prevalence and impact of nutritional abnormalities in IPF is currently unknown. Aims: NutrIPF (NCT03770845) is a prospective multicentre study that aims to investigate the NS and to identify nutritional phenotypes in a cohort of IPF patients at the time of disease diagnosis. Methods: Pts underwent a thorough pulmonary and nutritional evaluation including questionnaires on NS and physical activity, anthropometry, body impedence (BIA), dynamometry and blood tests. Results: 90 IPF pts (79% males, mean age 72.7 yrs) were enrolled. The majority of pts were prior smokers (62, 68.9%) with an inactive lifestyle according to International Physical Activity Questionnaire (IPAQ) score (39, 43.3%) and were classified as GAP stage 2 (47, 52.2%), with mean FVC% and DLCO% 86.5 and 54.2, respectively. In regards to nutritional phenotypes, the majority of pts were normonourished (67%), followed by obese (28%), sarcopenic (5%) and sarcopenic obese (1%). The majority of normonourished patients showed early signs of nutritional and physical performance alterations including overweight in 22% of cases, history of weight loss ≥ 5% in the prior 3 months in 12% of cases, reduction of gait speed in 12% of cases and a reduction of handgrip strenght in 40% of cases. At Mini Nutritional Assessment questionnaire 18% of pts were at risk of malnutrition. Conclusions: IPF pts at baseline are mainly normonourished and obese, but early signs of nutritional alterations and physical performance impairment can already be identified at this stage and impact on nutritional and rehabilitative interventions.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first identified as a novel coronavirus in Wuhan, Hubei province, central China, in December 2019, and is responsible for the 2019-to-present pandemic. According to the most recent data released by the World Health Organization, more than 200 million people have been infected by SARS-CoV-2 so far, and more than 4 million people died worldwide. Although our knowledge on SARS-CoV-2 and COVID-19 is constantly growing, data on COVID-19 in immunocompromised patients are still limited. The aim of the present systematic review is to describe clinical picture, disease severity, proposed treatment regimen, and response to vaccination in patients with different types and severity of immunosuppression.

The epidemic phase of Coronavirus disease 2019 (COVID-19) made the Worldwide health system struggle against a severe interstitial pneumonia requiring high-intensity care settings for respiratory failure. A rationalisation of resources and a specific treatment path were necessary. The study suggests a predictive model drawing on clinical data gathered by 119 consecutive patients with laboratory-confirmed COVID-19 admitted in Busto Arsizio hospital. We derived a score that identifies the risk of clinical evolution and in-hospital mortality clustering patients into four groups. The study outcomes have been compared across the derivation and validation samples. The prediction rule is based on eight simple patient characteristics that were independently associated with study outcomes. It is able to stratify COVID-19 patients into four severity classes, with in-hospital mortality rates of 0% in group 1, 6–12.5% in group 2, 7–20% in group 3 and 60–86% in group 4 across the derivation and validation sample. The prediction model derived in this study identifies COVID-19 patients with low risk of in-hospital mortality and ICU admission. The prediction model that the study presents identifies COVID-19 patients with low risk of in-hospital mortality and admission to ICU. Moreover, it establishes an intermediate portion of patients that should be treated accurately in order to avoid an unfavourable clinical evolution. A further validation of the model is important before its implementation as a decision-making tool to guide the initial management of patients.

OBJECTIVE:This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis.METHODS:Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes.RESULTS:Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P = .009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia.CONCLUSIONS:Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.

Alterations of cardiac autonomic control (CAC) are associated with poor outcomes in patients with infectious and non-infectious diseases. No evaluation of CAC in patients with community-acquired pneumonia (CAP) has been performed so far. The aim of the study was to assess CAC in patients with CAP and evaluate the impact of its alterations on disease severity and clinical outcomes in a multicenter, prospective, observational study.

Pneumonia is one of the main causes of morbidity and mortality in the elderly. The elderly population has exponentially increased in the last decades and the current epidemiological trends indicate that it is expected to further increase. Therefore, recognizing the special needs of older people is of paramount importance. In this review we address the main differences between elderly and adult patients with pneumonia. We focus on several aspects, including the atypical clinical presentation of pneumonia in the elderly, the methods to assess severity of illness, the appropriate setting of care, and the management of comorbidities. We also discuss how to approach the common complications of severe pneumonia, including acute respiratory failure and severe sepsis. Moreover, we debate whether or not elderly patients are at higher risk of infection due to multi-drug resistant pathogens and which risk factors should be considered when choosing the antibiotic therapy. We highlight the differences in the definition of clinical stability and treatment failure between adults and elderly patients. Finally, we review the main outcomes, preventive and supportive measures to be considered in elderly patients with pneumonia.

Identifying risk factors for exacerbations is a crucial step in the management of NCFBE patients. The aim of our study was to test etiology of bronchiectasis as risk factor for severe exacerbation requiring hospital admission. This was an observational, perspective study of consecutive NCFBE adult patients attending the outpatient bronchiectasis clinic at the San Gerardo University Hospital in Monza, Italy, during 2013. NCFBE etiology was assessed according to 2010 British Thoracic Society guidelines. A total of 162 patients (median age: 69 years; 42% males) were enrolled. Etiology prevalence is shown in Table 1. All etiologies were tested as risk factors for at least one hospitalization due to a severe exacerbation during 2013 (see Table 1). View this table: Table 1 Only NCFBE associated to COPD showed a statistically significant relation with the study outcome ( p -value: 0.04). COPD-related bronchiectasis patients should be strictly followed-up in order to prevent adverse outcomes.

The development of CCVE in patients with CAP might be influenced by the presence or absence of coronary atherosclerosis. To evaluate the incidence, risk factors and outcomes of hospitalized patients with CAP undergoing plaque-related vs. plaque-unrelated CCVE. An international, multicenter, prospective, observational study was performed on consecutive CAP patients hospitalized from Oct. 2009 to Oct. 2012 in 8 Respiratory Dpts. Among the 905 patients enrolled (59% males; median age: 76 years), the incidence of plaque-related and plaque-unrelated CCVE was 3% and 21% respectively [Table 1]. In-hospital mortality among patients who experienced plaque-related was higher in comparison to both those who experienced plaque-unrelated CCVE and the rest of the population (41% vs. 21% vs. 4%, p

Although NCFBE is a heterogeneous disease, patients may share common clinical features and could be, thus, clustered according to history, signs and symptoms. The aim of our study was to identify distinct clinical phenotypes of NCFBE patients according to clinical variables easily detectable during visits. This was an observational, prospective study of consecutive NCFBE patients attending the outpatient bronchiectasis clinic at the San Gerardo University Hospital in Monza, Italy, during 2013. A two-step cluster analysis was performed after having identified four key variables: dyspnea (evaluated by Medical Research Council –MRC- scale), daily sputum production, number of exacerbations, episodes of recurrent pneumonia (at least 1/year during the prior 3 years). Clusters were subsequently tested in a NCFBE population from Edinburgh, UK. A total of 161 patients (median age: 69 years; 42% males) were enrolled in Monza. Five clusters were identified (silhouette measure of cohesion and separation: 0.75; dimension rate: 4.00), see Figure 1. The number of patients with at least one hospitalization per year due to exacerbation was higher in the Poor Performance cluster than the other clusters (p

In the recently published Bronchiectasis Severity Index (BSI), radiological severity of non-CF bronchiectasis (NCFBE) has been assessed by a modified Reiff score (RS). A better accuracy of the BSI could be obtained if the more comprehensive Bhalla score (BS) will be used. To test this hypothesis, an observational, prospective study was performed on NCFBE patients at the bronchiectasis clinic of the San Gerardo University Hospital, Monza, Italy, during the year 2011. Both modified Reiff and Bhalla scores were calculated from chest HRCT scans by two external radiologists and compared among the BSI. The occurrence of at least one hospitalization for exacerbation during 2011 was the study outcome. Rounded averaged beta-coefficients of the BS identified by a Cox regression analysis were used to award points for the BSI score. The performance of the BSI including either the RS or the BS for hospital admission was assessed using the area under the receiver operator characteristic curve (ROC). A total of 146 consecutive NCFBE patients (48% males; median age: 68 years) were enrolled. Median values of the RS and BS in the study population were 6 and 19, respectively. 0 points were given for a RS <3 and 1 for a RS of 3+, as originally indicated. 0 points were given for a BS of 1-10, 5 points for 11-32 and 8 points for 33+. The ROC of the BSI for the study outcome was 0.88 and 0.87 including the RS or BS, respectively. The use of a more comprehensive score does not seem to improve the weight of radiological severity within the BSI in NCFBE patients.

The role of cardiac autonomic control (CAC) in the development of cardiovascular events (CVE) and adverse outcomes in community-acquired pneumonia (CAP) has not been yet investigated. To evaluate the impact of alteration of CAC on early and late outcomes, including CVE, in CAP. Consecutive patients hospitalized at two university hospitals from Sept. 2011 to Jan. 2013 for CAP were prospectively enrolled. Patients underwent 15' registration of ECG and respiration within 24 hours after admission. CAC was assessed using linear spectral (SP) and non-linear symbolic (SY) analysis of heart rate variability (HRV). SP evaluates rhythmical components of HRV, identifying three oscillations: very low (VLF), low (LF) and high (HF) frequency components. LF and HF are markers of sympathetic and vagal modulation, respectively. SY identifies 0V% and 2UV%, indices of sympathetic and vagal modulation, respectively. HRV indices were correlated with time to reach clinical stability (TCS) and a combined adverse outcome, including either CVE or mortality, during hospitalization. Fifty-eight patients (33 males; median age: 74 yrs) were enrolled. Patients with a TCS>3 days (n=38) showed a smaller VLF component on admission compared to patients with a TCS≤3 days (p= 0.03). Patients with adverse outcome (n=7) had lower LFnu (p=0.02) and higher 2UV% (p=0.002) values compared to patients without an adverse outcome. No other HRV indices were correlated with both outcomes. CAP patients with lower VLF on admission show a longer TCS during hospitalization. A predominant parasympathetic modulation and a reduced sympathetic oscillation on admission are predictors of adverse outcomes in CAP patients.

No data evaluated cardiovascular autonomic control (CAC) in community-acquired pneumonia (CAP). Aim was to describe CAC according to the severity of CAP. Patients hospitalized in two university hospitals from Sept. 2011 to Jan. 2013 for CAP underwent 159 registration of ECG and respiration within 24 hours after admission. CURB65, gas exchange and the presence of severe CAP (sCAP ATS 2007) were recorded on admission. CAC was assessed using spectral (SP) and symbolic (SY) analysis of heart rate variability (HRV). SP evaluates rhythmical components of HRV identifying two oscillations: low (LF) and high (HF) frequency components, markers of sympathetic and vagal modulation, respectively. SY identifies two indices, 0V% and 2UV%, indices of sympathetic and vagal modulation, respectively. 58 patients (33 males; median age: 74 yrs) were enrolled. sCAP patients showed a higher HR (p=0.036), lower 0V% and higher 2UV% compared to patients without sCAP. Patients with CURB65 score≥3 were characterized by lower LFnu compared to patients with CURB65 CAP patients with a severe disease on admission show a relatively predominant vagal modulation associated with an altered sympathetic modulation, possibly due to the loss of rhythmical properties of sympathetic outflow.