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.

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.

Feasibility and clinical impact of a portable bi-level ventilation device in patients with severe chronic obstructive pulmonary disease and exertional dyspnea: preliminary results from a clinical series.

We explore home use of a portable bi-level ventilation device among patients with severe chronic obstructive pulmonary disease (COPD), and describe changes in the patients' physical activity levels, perceived dyspnea, anxiety and depression, as well as their satisfaction with the device, after one month of use. METHODS: Forty patients with severe COPD and exertional dyspnea were instructed to use VitaBreath® device (Philips, Respironics) during efforts or activities of daily living for 4 weeks, and agreed to answer questionnaires on anxiety, depression, dyspnea and physical activity. RESULTS: Twenty-six (65%) patients used the VitaBreath® device for four weeks, while 14 patients (35%) stopped early for various reasons. Among patients who completed the 4-week course, no differences in dyspnea and physical activity were observed between baseline and follow-up (p-values 0.41 and 0.19, respectively). Thirteen (50%) and 15 (57%) patients experienced reduced anxiety and depression, respectively. Patients with greater functional impairment and less autonomy in activities of daily living tended to view the device more positively. CONCLUSION: Home use of portable bi-level positive-pressure ventilation devices by patients with COPD may alleviate disease-related anxiety and depression, particularly in more severe cases of COPD. Future portable device design should feature adjustable inspiratory/expiratory pressures.

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.

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). The 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 were 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: 19% in the non-IPF group and 43% in the IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers, such as neutrophilia on the differential blood cell count (HR 1.02 (CI 1.01-1.04)), the presence of pulmonary hypertension (HR 1.85 (CI 1.17-2.92)), and the diagnosis of IPF (HR 2.31 (CI 1.55-3.46)), resulted in negative prognostic factors in our analysis. Otherwise, lymphocytosis on the 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.

Derivation and validation of a prediction model for histopathologic fibrotic hypersensitivity pneumonitis.

BACKGROUND: Clinical differentiation of fibrotic hypersensitivity pneumonitis (f-HP) remains challenging given variable and overlapping presentations with other fibrotic interstitial lung disease (f-ILD). OBJECTIVE: We derived a multivariable model for predicting histopathologic f-HP to better inform multidisciplinary team discussion (MDD) diagnosis, particularly when biopsy may be unsafe or cannot be achieved. METHODS: Patients with histopathologically-defined f-HP and other overlapping f-ILD were reviewed for distinguishing clinical and radiological variables. Using elastic net logistic regression, a penalized regression approach to minimize overfitting, a clinical model built on non-invasive assessments was derived for the prediction of histopathologic f-HP. This model was then validated in an independently derived external cohort from three sites. RESULTS: The derivation and validation cohorts consisted of 248 (84 cHP and 164 other f-ILD) and 157 (82 f-HP and 75 other f-ILD) histopathologically-defined patients, respectively (total study N = 405). Variables retained from the elastic net model included age in years (regression coefficient 0.033), male sex (-1.109), positive exposure history (1.318), percent predicted forced vital capacity (-0.021), radiologic peribronchovascular axial ILD distribution (0.199), mid (-0.22) or lower lobe (-0.839) craniocaudal or patchy (0.287) ILD distribution, upper (1.188) or equivalent upper and lower lobe (0.237) traction bronchiectasis, mosaic attenuation (1.164), and centrilobular nodules (2.045). Bias corrected AUC was 0.84 (standard error = 0.02) for the derivation cohort and 0.80 (CI 0.73-0.87) for the validation cohort. CONCLUSIONS: This multivariable model demonstrated good predictive performance for delineating histopathologically-defined f-HP from other f-ILD as a means of avoiding or justifying biopsy and supporting MDD diagnostic confidence.

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.

Noninvasive Ventilatory Support of Patients with COVID-19 outside the Intensive Care Units (WARd-COVID).

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited.Objectives: To describe the prevalence and clinical characteristics of patients with COVID-19 treated with NIV outside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death).Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy.Results: We collected data on demographic and clinical characteristics, ventilatory management, and patient outcomes. Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio <150 mm Hg. Higher C-reactive protein and lower PaO2/FiO2 and platelet counts were independently associated with increased risk of NIV failure.Conclusions: The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success >60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/FiO2, and platelet counts were independently associated with increased risk of NIV failure.Clinical trial registered with ClinicalTrials.gov (NCT04382235).

Rituximab Versus Cyclophosphamide for Central Nervous System Involvement of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Case Series.

OBJECTIVE: To compare the effectiveness of rituximab (RTX) with cyclophosphamide (CYC) in patients who have central nervous system (CNS) involvement in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: A computer-assisted search was conducted to identify all adults who received a diagnosis of AAV with CNS involvement from January 1, 1997, through July 1, 2017, at our institution. RESULTS: Of the 17 patients identified, 11 had received RTX, and 6 had received CYC. Age at diagnosis of CNS involvement was similar in both groups. In the RTX group, 91% of the patients were women; in the CYC group, 33% were women (p = 0.03). At the time of CNS presentation, orbital involvement had occurred in 6 patients in the RTX group and in none of the patients in the CYC group. Initial remission of induction was achieved in all patients (100%) in the CYC group and in 10 patients (91%) in the RTX group. Two patients had no response to RTX: 1 patient when RTX was used for remission induction at the time of diagnosis and the second patient when RTX was used for remission induction after relapse. The median follow-up was 38 months (range, 9-127 months). Central nervous system relapse occurred in 4 patients in the RTX group and in 1 patient in the CYC group. Of the 4 patients in the RTX group with relapse, 3 had marked ocular involvement. Both nonresponder patients in the RTX group had ocular involvement. CONCLUSION: Rituximab is as effective as CYC in remission induction in patients with CNS involvement in AAV.

Progressive Fibrosing Interstitial Lung Diseases: Prevalence and Characterization in Two Italian Referral Centers.

BACKGROUND: The prevalence and natural history of progressive fibrosing interstitial lung diseases (PF-ILDs), and their response to commonly used treatments in real life are largely unknown. OBJECTIVES: The aim of the study was to describe the prevalence, clinical characteristics, management, and outcomes of PF-ILD patients attending 2 Italian referral centers (San Gerardo Hospital, Monza, and San Giuseppe Hospital, Milan) from January 1, 2011, to July 31, 2019. METHODS: From a cohort of non-idiopathic pulmonary fibrosis fibrosing ILD patients with at least 2-year follow-up, we selected only those with progressive disease, defined as per the INBUILD trial, collecting their demographical, clinical, and functional data. RESULTS: Out of the 245 fibrosing ILD patients, 75 (31%) were classified as PF-ILDs (median age 66 years, 60% males), most frequently idiopathic non-specific interstitial pneumonia (28%), followed by connective tissue disease-associated ILD (20%), chronic hypersensitivity pneumonitis, and sarcoidosis (17% each). Most patients (81%) were categorized as PF-ILDs because of forced vital capacity (FVC) decline ≥10%, while 19% experienced a marginal FVC decline (between 5 and 10%) associated with worsening respiratory symptoms or increasing extent of fibrotic changes on high-resolution computed tomography. Disease progression occurred after a median of 18 months from ILD diagnosis. The vast majority (93%) of PF-ILD patients received prednisolone, alone (40%) or associated with steroid-sparing agents (52%), and 35% of treated patients developed treatment-related adverse events. After ILD progression, the median survival was 3 (interquartile range (IQR) 2-5) years, with a 2- and 3-year mortality rate of 4 and 20%, respectively. CONCLUSIONS: In a real-life setting, approximately one-third of the fibrosing ILD patients showed a progressive course despite treatment. Studies aimed to better phenotype this subgroup of patients are needed.

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.

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.