Twelve-month clinical, functional, and radiological outcomes in patients hospitalized for SARS-CoV-2 pneumonia.

To assess long-term clinical, radiological, and functional follow-up of patients hospitalized for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia of different grades of severity. Two-hundred-thirty and three patients (Group 1, patients needed invasive mechanical ventilation, n = 69; Group 2, patients needed noninvasive mechanical ventilation, n = 78; Group 3, patients needed <12 L/min of O2 supply, n = 96) with a postdischarge follow-up >12 months were studied. Follow-up visits, chest computed tomography (CT) scan and pulmonary function tests (diffusing capacity of the lung for carbon monoxide [DLCO], 6-min walking tests [6MWT], spirometry) were done at 3, 6, and 12 months after discharge. Male sex was more frequent in Group 1 (n = 50, 72.5%) compared with Group 2 (n = 49, 62.5%) and Group 3 (n = 44, 51.2%), p = 0.024. Group 2 patients had more comorbidities and higher BMI compared with others. At Month 12, the main reported symptoms were fatigue (mainly in Group 3) and dyspnea; most symptoms resolved during follow-up, except brain fog, memory loss, and anosmia/dysgeusia that, when present at Month 3, usually persisted at Month 12. DLCO and 6MWT normalized at Month 12 in almost all patients. Only nine patients (13%) in Group 1 had a normal chest CT at Month 12, while 20 (29%) had >3 abnormalities, compared with 14 (17.9%) in Group 2 and 11 (11.4%) in Group 3, respectively (p = 0.04). Different clinical symptoms persist up to 12 months in patients hospitalized for SARS-CoV-2 pneumonia. Despite the persistence of abnormalities at chest CT scan after 12 months, an impairment of pulmonary function persists only in a minority of subjects. A longer follow-up is needed to assess the evolution of radiological abnormalities in COVID-19 population.

Sarcopenia in idiopathic pulmonary fibrosis: a prospective study exploring prevalence, associated factors and diagnostic approach.

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.

One-year pulmonary impairment after severe COVID-19: a prospective, multicenter follow-up study.

BACKGROUND: Long-term pulmonary sequelae following hospitalization for SARS-CoV-2 pneumonia is largely unclear. The aim of this study was to identify and characterise pulmonary sequelae caused by SARS-CoV-2 pneumonia at 12-month from discharge. METHODS: In this multicentre, prospective, observational study, patients hospitalised for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only", "continuous positive airway pressure (CPAP)" and "invasive mechanical ventilation (IMV)") and followed up at 12 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6 min walking test, high resolution CT (HRCT) scan, and modified Medical Research Council (mMRC) dyspnea scale were collected. RESULTS: Out of 287 patients hospitalized with SARS-CoV-2 pneumonia and followed up at 1 year, DLCO impairment, mainly of mild entity and improved with respect to the 6-month follow-up, was observed more frequently in the "oxygen only" and "IMV" group (53% and 49% of patients, respectively), compared to 29% in the "CPAP" group. Abnormalities at chest HRCT were found in 46%, 65% and 80% of cases in the "oxygen only", "CPAP" and "IMV" group, respectively. Non-fibrotic interstitial lung abnormalities, in particular reticulations and ground-glass attenuation, were the main finding, while honeycombing was found only in 1% of cases. Older patients and those requiring IMV were at higher risk of developing radiological pulmonary sequelae. Dyspnea evaluated through mMRC scale was reported by 35% of patients with no differences between groups, compared to 29% at 6-month follow-up. CONCLUSION: DLCO alteration and non-fibrotic interstitial lung abnormalities are common after 1 year from hospitalization due to SARS-CoV-2 pneumonia, particularly in older patients requiring higher ventilatory support. Studies with longer follow-ups are needed.

Clinical Characteristics of COVID-19 Patients With Gastrointestinal Symptoms in Northern Italy: A Single-Center Cohort Study.

INTRODUCTION: The most typical presentation of COVID-19 is an acute respiratory syndrome whose most common symptoms include fever, cough, and dyspnea. However, gastrointestinal symptoms, such as diarrhea and nausea/vomiting, are increasingly reported in patients affected by COVID-19. This study aimed to describe the prevalence and time of onset of gastrointestinal symptoms in patients affected by COVID-19 and to find potential associations between gastrointestinal symptoms and clinical outcomes. METHODS: We performed a prospective single-center cohort study, enrolling patients who received diagnosis of COVID-19 at our institution between March 23, 2020, and April 5, 2020. We collected patient demographics and medical history, laboratory data, and clinical outcomes. Furthermore, we used a specifically designed questionnaire, administered to patients at time of diagnosis, to obtain data on the presence and time of onset of fever, typical respiratory symptoms, gastrointestinal symptoms, and other symptoms (fatigue, headache, myalgia/arthralgia, anosmia, ageusia/dysgeusia, sore throat, and ocular symptoms). RESULTS: In our cohort, 138 (69%) of 190 patients showed at least 1 gastrointestinal symptom at diagnosis; if excluding hyporexia/anorexia, 93 patients (48.9%) showed at least 1 gastrointestinal symptom. Gastrointestinal symptoms, in particular diarrhea, were associated with a lower mortality. At multivariate analysis, diarrhea was confirmed as independent predictive factor of lower mortality. DISCUSSION: Gastrointestinal symptoms are very frequent in patients with COVID-19 and may be associated with a better prognosis. These data suggest that, in some patients, the gastrointestinal tract may be more involved than the respiratory system in severe acute respiratory syndrome coronavirus 2 infection, and this could account for the less severe course of disease.

Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study.

BACKGROUND: Long-term pulmonary sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia are not yet confirmed; however, preliminary observations suggest a possible relevant clinical, functional, and radiological impairment. OBJECTIVES: The aim of this study was to identify and characterize pulmonary sequelae caused by SARS-CoV-2 pneumonia at 6-month follow-up. METHODS: In this multicentre, prospective, observational cohort study, patients hospitalized for SARS-CoV-2 pneumonia and without prior diagnosis of structural lung diseases were stratified by maximum ventilatory support ("oxygen only," "continuous positive airway pressure," and "invasive mechanical ventilation") and followed up at 6 months from discharge. Pulmonary function tests and diffusion capacity for carbon monoxide (DLCO), 6-min walking test, chest X-ray, physical examination, and modified Medical Research Council (mMRC) dyspnoea score were collected. RESULTS: Between March and June 2020, 312 patients were enrolled (83, 27% women; median interquartile range age 61.1 [53.4, 69.3] years). The parameters that showed the highest rate of impairment were DLCO and chest X-ray, in 46% and 25% of patients, respectively. However, only a minority of patients reported dyspnoea (31%), defined as mMRC ≥1, or showed restrictive ventilatory defects (9%). In the logistic regression model, having asthma as a comorbidity was associated with DLCO impairment at follow-up, while prophylactic heparin administration during hospitalization appeared as a protective factor. The need for invasive ventilatory support during hospitalization was associated with chest imaging abnormalities. CONCLUSIONS: DLCO and radiological assessment appear to be the most sensitive tools to monitor patients with the coronavirus disease 2019 (COVID-19) during follow-up. Future studies with longer follow-up are warranted to better understand pulmonary sequelae.

Management of Chronic Respiratory Failure in Interstitial Lung Diseases: Overview and Clinical Insights.

Interstitial lung diseases (ILDs) may be complicated by chronic respiratory failure (CRF), especially in the advanced stages. Aim of this narrative review is to evaluate the current evidence in management of CRF in ILDs. Many physiological mechanisms underlie CRF in ILDs, including lung restriction, ventilation/perfusion mismatch, impaired diffusion capacity and pulmonary vascular damage. Intermittent exertional hypoxemia is often the initial sign of CRF, evolving, as ILD progresses, into continuous hypoxemia. In the majority of the cases, the development of CRF is secondary to the worsening of the underlying disease; however, associated comorbidities may also play a role. When managing CRF in ILDs, the need for pulmonary rehabilitation, the referral to lung transplant centers and palliative care should be assessed and, if necessary, promptly offered. Long-term oxygen therapy is commonly prescribed in case of resting or exertional hypoxemia with the purpose to decrease dyspnea and improve exercise tolerance. High-Flow Nasal Cannula oxygen therapy may be used as an alternative to conventional oxygen therapy for ILD patients with severe hypoxemia requiring both high flows and high oxygen concentrations. Non-Invasive Ventilation may be used in the chronic setting for palliation of end-stage ILD patients, although the evidence to support this application is very limited.

Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.

BACKGROUND: Interstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs. METHODS: A literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017). RESULTS: In managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out. Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients' therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF. CONCLUSIONS: Despite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients' management, possibly leading to improved outcomes. However, further studies are warranted.

Coexistence of Eosinophilic Granulomatosis With Polyangiitis and Allergic Bronchopulmonary Aspergillosis: A Fascinating Relationship.

Elevated eosinophil counts are associated with various diseases, including eosinophilic granulomatosis with polyangiitis (EGPA) and allergic bronchopulmonary aspergillosis (ABPA). EGPA is a rare small-vessel vasculitis characterized by asthma, eosinophilia, fleeting pulmonary infiltrates, and systemic manifestations. ABPA, initiated by immune reactions against Aspergillus fumigatus in the airways, presents with poorly controlled asthma, wheezing, hemoptysis, productive cough, and systemic symptoms, which result in characteristic central bronchiectasis. Fleeting pulmonary opacities are common radiologic findings. We present a case of ABPA in a patient with a prior EGPA diagnosis under treatment with mepolizumab 300 mg monthly and review eight similar cases from the literature. In these cases, EGPA and ABPA diagnoses preceded each other or were concurrent. Treatment of the latter improved control of both diseases. IL-5 is pivotal in EGPA pathogenesis, and mepolizumab, targeting IL-5, has been effective in EGPA treatment. Our patient received mepolizumab for EGPA and continued it post-ABPA diagnosis, showing favorable outcomes. This suggests mepolizumab as a therapeutic link between EGPA and ABPA. Mepolizumab therapy holds promise for managing both EGPA and ABPA. Double-blind placebo-controlled studies are warranted to establish its efficacy and safety for ABPA, emphasizing the need for further research in this area.

Nutritional assessment in idiopathic pulmonary fibrosis: a prospective multicentre study.

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.

Nontuberculous mycobacterial pulmonary disease: an integrated approach beyond antibiotics.

Nontuberculous mycobacterial (NTM) pulmonary disease (PD) is an emerging condition with heterogeneous manifestations from both the microbiological and the clinical point of view. Diagnostic and therapeutic guidelines are available but there are still unmet patients' and physicians' needs, including therapy-related adverse events, symptom control, management of comorbidities, risk of re-exposure to the pathogen and unfavourable outcomes. In the present review, we provide currently available evidence for an integrated approach to NTM-PD beyond antibiotic therapy. This includes 1) avoiding exposure to environments where mycobacteria are present and careful evaluation of lifestyle and habits; 2) implementing a personalised pulmonary rehabilitation plan and airway clearance techniques to improve symptoms, exercise capacity, health-related quality of life (QoL) and functional capacity in daily living activities; 3) a nutritional evaluation and intervention to improve health-related QoL and to control gastrointestinal side-effects during antimicrobial therapy, particularly in those with low body mass index and history of weight loss; and 4) managing comorbidities that affect disease outcomes, including structural lung diseases, immune status evaluation and psychological support when appropriate.

Predictors of Worse Prognosis in Young and Middle-Aged Adults Hospitalized with COVID-19 Pneumonia: A Multi-Center Italian Study (COVID-UNDER50).

Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in the overall COVID-19 population, but limited information is available on their roles in young and middle-aged adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics and role of selected prognostic predictors in a large cohort of young and middle-aged hospitalized patients. Nine pulmonology units, across north and center of Italy, were involved in this retrospective study. Comorbidities were classified according to their known or potential association with COVID-19. A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 27.7%, and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only independent, significant predictors for MV. Comorbidities, such as hypertension, diabetes, asthma, and increased D-dimer levels were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Obesity in young and middle-aged adults is a strong predictor of a more complicated COVID-19, without, however, evidence of a significant effect on in-hospital mortality. Selected comorbidities, including hypertension, diabetes and asthma, significantly impact survival even in a younger population, suggesting the need for prompt recognition of these conditions.

Healthy Promotion for Fighting Metabolic Syndrome: Insights from Multi-Center HeRO-FiT Cohort.

We know that metabolic syndrome (MS) is a modern cardiovascular (CV) "epidemic", especially in western populations. MS is indeed strictly related to the risk of developing CV diseases (CVD) and/or diabetes. Therefore, the aim of our multi-center study was to promote a "healthy style" for fighting MS. Each participating center analyzed its own database of outpatients and globally we have pulled out 100 volunteers to participate in the study. Before starting, we collected their written consent. Enrolled subjects have not any history of overt CVD and/or diabetes, but they matched National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP) criteria for MS. After enrolment (t0), subjects were randomly divided into two homogeneous groups: a) only diet suggestions; b) both diet and exercise prescription. Later, we measured for each subject: blood pressure (BP), heart rate (HR), height, weight, body mass index (BMI), waist circumference (WC), waist hip ratio (WHR), six-minute walking test (WT6M), distance and common blood tests such as fasting plasma glucose, high-density lipoproteins (HDL) and triglycerides (T1 assessments). At six months (T2), the same parameters were measured and then statistical comparisons were performed. Attention to diet caused significant changes only in WC and WHR, whilst a coupling of exercise and diet revealed a statistically significant improvement in HR, BP, BMI, blood samplings and WT6M too. In conclusion, a healthy lifestyle should be more encouraged by physicians and/or collaborators (such as dieticians) operating in preventive settings. Diet and physical activity may be early useful strategies in the "battle" against MS even before any medication choices. Further studies will be necessary in order to better address the topic.

Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy.

Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that binds to free IL-5. It induces bone marrow eosinophil maturation arrest and decreases eosinophil progenitors and subsequent maturation in the blood and bronchial mucosa. Its use has been extensively studied in severe eosinophilic asthma at a dose of 100 mg subcutaneously (SC) every 4 weeks and, more recently, in other hypereosinophilic syndromes. Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophilic vasculitis that may involve multiple organs. Characteristic clinical manifestations are asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Among the numerous pathways involved in the pathogenesis of EGPA, the Th-2 phenotype has a main role, as suggested by the prominence of the asthmatic component, in triggering the release of key cytokines for the activation, maturation and survival of eosinophils. In particular, IL-5 is highly increased in active EGPA and its inhibition can represent a potential therapeutic target. In this scenario, mepolizumab may play a therapeutic role. After some positive preliminary observations on the use of mepolizumab in small case series of EGPA patients with refractory or relapsing disease despite standard of care treatment, a randomized controlled trial was published in 2017. Mepolizumab at a dose of 300 mg administered by SC injection every 4 weeks proved effective in prolonging the period of remission of the disease, allowing for reduced steroid use. The positive results of this study, which met both of the primary endpoints, led to the approval in the USA of mepolizumab in adult patients with EGPA by the Food and Drug Administration in 2017. Therefore, mepolizumab can be officially considered as an add-on therapy with steroid-sparing effect in cases of relapsing or refractory EGPA. However, the most appropriate dose and duration of therapy still need to be determined. Future studies on larger multinational populations with prolonged follow-up are warranted.

Long-term macrolides in diffuse interstitial lung diseases.

In the present review we provide currently available evidence for the use of macrolides in the treatment of diffuse interstitial lung diseases (ILDs). Up to now, research on macrolides has mainly focused on three areas. First, macrolides have shown some promising results in cellular models and case reports as antifibrotic agents, by promoting autophagy and clearance of intracellular protein aggregates and acting as regulators of surfactant homeostasis. Secondly, macrolides have an immunomodulatory effect, which has been applied in some organising pneumonia cases. In particular, macrolides have been tested in association with systemic corticosteroids as steroid-sparing agents and alone as either first-line agents in mild cases or second-line agents where steroids were poorly tolerated or had failed. Thirdly, a recent area of research concerns the possible role of macrolides as modulators of lung microbiota and the host-microbiota interaction. This function has been particularly studied in idiopathic pulmonary fibrosis patients, in whom changes in microbiota have been proved to be associated with disease progression. However, the lack of high-quality studies makes the application of macrolide therapy in ILDs a field in which research should be conducted on a large scale.