Diagnostic delay in bronchiectasis: an Italian perspective.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Use of 6-minute walk distance to predict lung transplant-free survival in fibrosing non-IPF interstitial lung diseases.

BACKGROUND AND OBJECTIVE: The identification of progression in patients with fibrosing non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs) represents an ongoing clinical challenge. Lung function decline alone may have significant limitations in the detection of clinically significant progression. We hypothesized that longitudinal changes of 6-min walk distance (6MWD) from baseline, simultaneously considered with measures of lung function, may independently predict survival and identifying clinically significant progression of disease. METHODS: Forced vital capacity (FVC), diffusing lung capacity (DLCO) and 6MWD were considered both at baseline and at 1 year in a discovery cohort (n = 105) and in a validation cohort (n = 138) from different centres. The primary endpoint was lung transplant (LTx)-free survival. RESULTS: Average follow-up was 3 years in both cohorts. Combined incidence of deaths and LTx was 29% and 21%, respectively. No collinearity and no strong correlations were observed among FVC, DLCO and 6MWD longitudinal changes. While age, gender and BMI were not significant, 6MWD decline ≥24 m predicted LTx-free-survival significantly and independently from FVC and DLCO declines, with high sensitivity and specificity, in both the discovery and the validation cohorts. Although FVC and DLCO declines remained significant predictors of LTx-free survival, 6MWD decline was more accurate than the proposed ATS/ERS/JRS/ALAT functional criteria. Results were confirmed after stratifying patients by baseline FVC. CONCLUSION: Longitudinal declines of 6MWD are associated with poor survival in fibrosing ILDs across a wide range of baseline severity, with high accuracy. 6MWD longitudinal decline is largely independent from lung function decline and may be integrated into the routine assessment of progression.

Two-year cardio-pulmonary follow-up after severe COVID-19: a prospective study.

Short- and medium-term cardio-pulmonary sequelae after COVID-19 have been extensively studied. However, studies with longer follow-ups are required. This study aims to identify and characterise cardio-pulmonary sequelae, in patients hospitalised for SARS-CoV-2 pneumonia, at 24 months follow-up. This is a prospective, observational cohort study conducted on consecutive patients hospitalised for COVID-19 and acute respiratory failure. Patients were followed up at 24 months with complete pulmonary function tests (PFTs), 6-min walking test and a dyspnoea score (Modified Medical Research Council scale). A subgroup of patients with at least one clinical or functional sign suggestive of increased pulmonary pressures also underwent transthoracic echocardiography (TTE) to evaluate the presence of direct or indirect signs of pulmonary hypertension (PH). Ninety consecutive patients (74% men, median age 59.1 years) were enrolled in the study. In regard to PFTs, carbon monoxide diffusion capacity (DLCO) impairment was observed in 23 cases (26%), in all cases of mild entity. When considering the dyspnoea, 30 (34%) patients showed some degree of breathlessness. Forty patients underwent TTE. No patients had overt PH or chronic thromboembolic PH. However, all patients showed a hyperdynamic state of the right ventricle, and 8 (20%) patients had a decreased acceleration time on pulmonary valve, signs of increased pulmonary vasculature resistances and afterload elevation. At 24-month follow-up after severe COVID-19, DLCO and TTE prove to be the most sensitive tool to detect cardio-pulmonary sequelae. Dyspnoea is still present in about one-third of patients and requires a multidisciplinary approach.

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

INTRODUCTION: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. RESULTS: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting ß2-agonists and the association inhaled corticosteroids/long-acting ß2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. CONCLUSIONS: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

The usual Interstitial pneumonia pattern in autoimmune rheumatic diseases.

Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs.

Concurrent features of sarcoidosis and hypersensitivity pneumonitis in two patients exposed to fungal antigens.

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis (HP) are two distinct clinical entities that share granulomatous inflammation, although each of them has specific clinical, radiologic and pathologic profiles. Coexistence of the two diseases have been described, suggesting, at least in some cases, a common biologic background. CASE PRESENTATION: We describe two patients showing the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis. Case 1: a 51-year old never smoker man had a history of occupational exposure, episodes of acute exacerbations and positive serum precipitins to Penicillium spp suggestive of HP, while the positivity of serum angiotensin converting enzyme (ACE) favored sarcoidosis. Case 2: a 42-year old non-smoker woman with occasional finding of enlarged mediastinal lymph nodes had a history of domestic exposure to molds and positive serum precipitins to Aspergillus spp suggestive of HP. In both cases high resolution computed tomography (HRCT) together with broncoscopy findings allowed to maintain both the diagnoses: HRCT showed both enlarged hilar/mediastinal limph nodes and intersitial lung involvement typical of HP; bronchoalveolar lavage presented marked lymphocytosis and granulomatous nodal lesions were observed at transbronchial needle aspiration. CONCLUSIONS: Sarcoidosis and HP share some clinical findings and the differential diagnosis may be difficult. Our cases suggest that a common trait may be responsible for the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis in the same patient.

Late onset toxicities associated with the use of CDK 4/6 inhibitors in hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer patients: a multidisciplinary, pan-EU position paper regarding their optimal management. The GIOCONDA project.

The personalization of therapies in breast cancer has favoured the introduction of new molecular-targeted therapies into clinical practice. Among them, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have acquired increasing importance, with the approval in recent years of palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy. Currently, no guidelines are available to monitor and manage potential long-term toxicities associated with the use of these drugs. A multidisciplinary panel of European oncologists, was supported by a pharmacologist, a hematologist, a hepatologist and a pulmonologist to discuss the management of long-term toxicities, based on the literature review and their clinical experience. The panel provided detailed roadmaps to manage long-term toxicities associated with the use of CDK4/6 inhibitors in clinical practice. Knowing the frequency and characteristics of the toxicity profile associated with each CDK4/6 inhibitor is important in the decision-making process to match the right drug to the right patient.

Idiopathic interstitial pneumonia in a patient with von Hippel-Lindau syndrome: a first case.

Although the mechanisms are not known, this is a case of progressive interstitial lung involvement, with a NSIP radiological pattern, evolving in pulmonary fibrosis in a patient with von Hippel-Lindau syndrome, without extrapulmonary fibrosis. https://bit.ly/3QlNStu.

Healthcare costs and resource utilisation in bronchiectasis, asthma and COPD.

Direct healthcare costs for patients with asthma are less than half (-52%) and for patients with COPD are 41% higher if compared to those of patients with bronchiectasis. The leading expense items in bronchiectasis are hospitalisations and antibiotics. https://bit.ly/3Iq8AUP.

Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population.

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.

Effectiveness and economic impact of Dupilumab in asthma: a population-based cohort study.

RATIONALE: Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed. OBJECTIVES: To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation ("post-intervention period") and (i) the 6 months before Dupilumab initiation ("wash-out period") and (ii) the corresponding 6 months of the prior year ("pre-intervention period"). MAIN RESULTS: In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting ß2-agonists, inhaled corticosteroids (ICS)/long-acting ß2-agonists and ICS alone) when comparing the "pre-intervention" to the "post-intervention" period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the "pre-intervention" and "post-intervention" period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change. CONCLUSIONS: Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.

A multidisciplinary approach to screen the post-COVID-19 conditions.

BACKGROUND: Post-COronaVIrus Disease 2019 (COVID-19) conditions (PCC) include multiple symptoms afflicting different organs and systems. To evaluate the frequency and type of them, we described our multidisciplinary approach with preliminary results of the first enrolled patients. METHODS: We included patients aged ≥ 18 years with hospital admission for confirmed SARS-CoV-2 infection. Symptoms were grouped in five macro groups hereafter referred to as "Symptoms Category" (SC): respiratory SC (dyspnoea or cough), neurological SC (peripheral neuropathies, headache, impaired mobility, behavioural disorders), psychological SC (sleep disorders, mood disorders), muscular SC (arthromyalgia, asthenia), other SC (fever, alopecia, diarrhoea, weight loss, smell and taste alterations, sexual dysfunctions). SC were evaluated at discharge and at follow-up. Association between patients' characteristics and presence of SC at follow up was estimated by a logistic multivariable regression model. RESULTS: From June 2020 to July 2021, we followed up 361 patients: 128 (35.5%) who were previously admitted to Intensive Care Unit (ICU) and 233 patients to ordinary department. The median length of hospital stay was 20 days (Inter-Quartile-Range 13-32). Most patients (317/361, 87.8%) were still symptomatic at discharge, with one third referring three or more SC. At follow up, 67.3% (243/361) of patients still complained at least one SC. Moreover, 159 patients (44%) developed at least one new involved SC during follow up: 116 (72.9%) one SC, 39 (24.5%) two SC, 4 (2.5%) three or more SC. At follow up visit 130 of 361 (36%) were still with SC developed during follow up. At multivariable analysis presence of any SC at follow-up was associated with male gender (Odds Ratio [OR] 3.23, Confidence Interval [CI] 95% 1.46-7.15), ICU admission (OR 2.78, CI 95% 1.29-5.96) and presence of SC at discharge (OR 14.39, CI 95% 6.41-32.32). CONCLUSIONS: In our sample of patients with severe COVID-19, we found that PCC are highly variable and fluctuating over time; in particular, in about 50% of our patients new SC appear during follow up. Moreover, presence of PCC also in patients without SC at discharge and the variability of symptoms underlining the advisability of our multidisciplinary approach. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04424992, registered on 28 February 2020 https://www. CLINICALTRIALS: gov/ct2/results?recrs=ab&cond=&term=NCT04424992&cntry=&state=&city=&dist The current version of protocol is version 1.0 enrolling since June 2020. The enrollment is still ongoing.

Progression and prognosis of interstitial pneumonia with autoimmune features: a longitudinal, prospective, multi-centre study.

OBJECTIVES: To evaluate the rate of progression towards specific autoimmune diseases (SADs) of a prospective, multi-centre cohort of patients classifiable as interstitial pneumonia with autoimmune features (IPAF). METHODS: IPAF patients were enrolled based on specific research criteria, and jointly followed by rheumatologists and pulmonologists for at least one year with clinical check-ups, serological exams including autoimmunity, capillaroscopy and high-resolution computed tomography (HRCT). Diagnostic assessment was repeated at least once a year, or earlier when deemed useful. RESULTS: We enrolled 191 IPAF patients through 95 different combinations of IPAF criteria. Of these, 24.1% progressed towards SAD, mainly in connective tissue diseases but also in microscopic polyangiitis. The IPAF patients who progressed were younger than stable IPAF patients (63±10 years vs. 68±9 years, p=0.002) and had a longer follow-up (36.9±18.7 vs. 29.3±15.7 months, p=0.007), but similar severity. No parameters were associated with overall progression, but some parameters were associated with the development of specific diagnoses: Sjögren's syndrome with positivity for SSA (p=0.007, χ2 7.4); idiopathic inflammatory myopathy with mechanic's hands (p=<0.0001, χ2 12.6), organizing pneumonia pattern (p=0.01, χ2 6.1), positivity for anti-Pm/scl (p=0.04 χ2 4.1) and anti-MDA5 (p=0.04, χ2 4.2); systemic sclerosis with palmar telangiectasias (p=<0.0001 2 18.3), positivity for anti-Scl70 (p=<0.0001 χ2 12.5) and anti-PM/Scl (p=0.001 χ2 10.1). CONCLUSIONS: IPAF patients had a rate of progression towards SAD similar to that reported in previous studies on undifferentiated connective tissue diseases, thus including some patients in which lung involvement could represent the first or even the sole clinical manifestation of a SAD.

Frailty and long-COVID: is COVID-19 responsible for a transition in frailty status among older adults who survived hospitalization for COVID-19?

BACKGROUND: There is a paucity of knowledge about the effects of COronaVIrus Disease-19 (COVID-19) on long-term frailty development or progression over time. AIM: This study aims to assess transitions in frailty status in older adults who survived hospitalization for COVID-19. METHODS: This is a longitudinal panel study. A multidisciplinary outpatient follow-up service was established since summer 2020, for the evaluation of individuals discharged alive, after hospitalization due to COVID-19. Frailty status was assessed in-hospital and at follow-up using the clinical frailty scale (CFS). Main patients' characteristics, including health, functional, cognitive, and psychological status were collected. RESULTS: A total of 177 patients aged 65 years and older were evaluated until June 2022. They were predominantly male, with a median age of 70 (Q1-Q3 67-75) years and a median body mass index of 27.5 (Q1-Q3 24.9-30.6) kg/m2 at hospital admission. The median follow-up time was 6.3 (Q1-Q3 3.7-10.9) months. Sixty-one patients (34.5%) scored worse at CFS follow-up compared to hospital admission, and twenty-two patients (12.4%) became frail. DISCUSSION AND CONCLUSION: This study shows that one out of three older patients previously hospitalized for COVID-19 had an unfavorable transition in CFS score during a median follow-up of nearly 6 months. Specific interventions to prevent frailty development or progression should be considered for patients at risk. Further studies are required to confirm our findings.

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.

Immunomodulatory treatment of interstitial lung disease.

Interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) have an array of immunomodulatory treatment options compared with IPF, due to their inflammatory component. However, there is a relative paucity of guidance on the management of this heterogeneous group of diseases. In ILDs other than IPF, immunosuppression is the cornerstone of therapy, with varying levels of evidence for different immunomodulatory agents and for each specific ILD. Classification of ILDs is important for guiding treatment decisions. Immunomodulatory agents mainly include corticosteroids, mycophenolate mofetil (MMF), azathioprine, methotrexate, cyclophosphamide and rituximab. In this review, the available evidence for single agents in the most common ILDs is first discussed. We then reviewed practical therapeutic approaches in connective tissue disease-related ILD and interstitial pneumonia with autoimmune features, scleroderma-related ILD, vasculitis and dermatomyositis with hypoxemic respiratory failure, idiopathic non-specific interstitial pneumonia, hypersensitivity pneumonitis sarcoidosis, fibrosing organizing pneumonia and eosinophilic pneumonia. The treatment of acute exacerbations of ILD is also discussed. Therapy augmentation in ILD is dictated by the recognition of progression of disease. Criteria for the evaluation of progression of disease are then discussed. Finally, specific protocol and measures to increase patients' safety are reviewed as well, including general monitoring and serologic surveillance, Pneumocystis jirovecii prophylaxis, patients' education, genetic testing for azathioprine, MMF serum levels and cyclophosphamide administration protocols. Immunomodulatory therapies are largely successful in the management of ILDs and can be safely managed with the application of specific protocols, precautions and monitoring.