Serum Aspergillus-specific IgE, IgG and IgG4 immunoglobulins assessment in the work-up of invasive pulmonary aspergillosis: a prospective cohort study.

BACKGROUND: Positive microbiological fungal culture from bronchoalveolar-lavage-fluid (BAL) for Aspergillus or tissue biopsy and the detection of high levels of Aspergillus Galactomannan (GM) are commonly considered standard for diagnosing Invasive Pulmonary Aspergillosis (IPA). However, Aspergillus infection induces both cellular and humoral immune responses, characterized by the production of specific immunoglobulins, which can be easily detected in serum and accurately measured. This study hypothesized that Aspergillus-specific IgE, IgG, including IgG4, assays could be adopted as a rapid preliminary screening tool in patients with suspected Aspergillus-related lung disease in order to help in the identification of patients who require more invasive procedures (bronchoscopy, biopsy). METHODS: We prospectively stored 447 serum specimens of patients admitted for suspected IPA from 1 January 2010 to 31 July 2021. Serum total IgE and serum IgE, IgG and IgG4 specific for Aspergillus fumigatus and Aspergillus niger were determined for each sample. In addition, bronchoscopy with BAL for microbiologic culture and Aspergillus Galactomannan (GM) antigen were performed in all patients. RESULTS: Patients with IPA, diagnosed by detection of a positive BAL culture for Aspergillus and/or a positive GM, showed higher serum levels of specific Aspergillus fumigatus and Aspergillus niger immunoglobulins. Serum-specific Aspergillus fumigatus IgG at a cut-off of 22.6 mgA/L showed the highest sensitivity in predicting IPA, though quite moderate (AUC 0.62). Nonetheless, the simultaneous presence of values below the cut-off of Aspergillus IgE, IgG and IgG4 showed a negative predictive value greater than 90% both towards positive BAL culture and positive GM. CONCLUSIONS: In patients with suspected IPA, Aspergillus-specific immunoglobulins assay could be tested as a preliminary screening tool to support more invasive procedures, i.e. BAL.

Updated estimates of excess total mortality in Italy during the circulation of the BA.2 and BA.4-5 Omicron variants: April-July 2022.

BACKGROUND: The impact of new lineages and sub-lineages of Omicron on total and excess mortality is largely unknown. This study aims to provide estimates of excess mortality during the circulation of the Omicron variant in Italy updated to July 2022. METHODS: Over-dispersed Poisson regression models, fitted separately for men and women, on 2011-2019 mortality data were used to estimate the expected number of deaths during the Covid-19 pandemic. The excess deaths were then obtained by the difference between observed and expected deaths and computed at all ages and at working ages (25-64 years). RESULTS: Between April and June 2022, we estimated 9,631 excess deaths (+6.3%) at all ages (4,400 in April, 3,369 in May, 1,862 in June) and 12,090 in July 2022 (+23.4%). At working ages, the excess was 763 (+4.9%) in April-June 2022 and 679 (+13.0%) in July 2022. CONCLUSIONS: Excess total mortality persisted during the circulation of different lineages and sub-lineages of the Omicron variant in Italy. This excess was not limited to the elderly population but involved also working age individuals, though the absolute number of deaths was small. The substantial excess found in July 2022 is, however, largely attributable to high temperatures. At the end of the year, this may translate into 30 to 35,000 excess deaths, i.e. over 5% excess mortality. This reversed the long-term trend toward increasing life expectancy, with the relative implications in social security and retirement schemes.

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.

Enlightening chronic obstructive pulmonary disease through patients' and caregivers' narratives.

PURPOSE: The primary aim of this research was to raise awareness for COPD through real narratives of patients, caregivers, and pulmonologists. The second objective includes providing clinicians new means of caring for and treating patients with COPD. METHODS: Using narrative medicine, testimonies from patients, their caregivers, and clinicians were collected through an online questionnaire enriched by a narrative plot. Narrations were analyzed throughout descriptive statistics and an elaboration of recurring words and expressions. RESULTS: Throughout the project, 350 narratives were collected from 235 patients, 55 caregivers, and 60 physicians. Though a generally neutral reaction had been observed upon diagnosis, COPD had been found to have a high impact on the patients' and caregivers' lives. Metaphors utilized by patients and caregivers were suggestive of fear and panic unlike those utilized by clinicians who usually had a more technical approach. Smoking was a significant concern for not only patients and caregivers but also clinicians. CONCLUSION: Physicians are therefore challenged to find new ways of communicating COPD to raise awareness on this pathology and encourage corrective habits. An important social objective should be the implementation of a health system that is able to optimize patients' and caregivers' lives.

Epidemiology of clinical trials of medicines in respiratory diseases in Europe and Italy.

BACKGROUND: Clinical trials play a key role in advancing medical knowledge, improving patient care and promoting economic growth in Europe. We have assessed the clinical trial activity in any respiratory diseases in Europe, with a specific focus on Italy. METHODS: Information from public sources (EFPIA, clinicaltrials.gov, clinicaltrialsregister. eu, AIFA) was used to describe clinical trial activity of in respiratory diseases in Europe and by country. RESULTS: In 2015, 3908 clinical trials were reported in Europe, 386 in respiratory diseases (9.9%). Germany was the first country both as absolute number (76 trials) and as percentage within country trials (14%), followed by Poland. Spain, Italy and France were the countries with the lowest number and percentage of trials in respiratory diseases. In 2013, the Italian Drug Agency reported 9 trials with respiratory compounds in Italy (2.1% of overall trials, 12ˆ position in the therapeutic area rank), 33% in phase 2 and 66% in phase 3. No phase 1 or phase 4 trials were reported for respiratory trials. Prevalence of respiratory trials by non-profit sponsors (28.3%) was below the average for the country (38.3%). CONCLUSIONS: Europe has a greater potential for clinical research on drugs for respiratory diseases, particularly in countries with less activity, such as Spain, France and Italy, that should identify and implement actions to increase attractiveness for clinical trials of drugs.

Asthma management in a specialist setting: Results of an Italian Respiratory Society survey.

BACKGROUND: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. AIM: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. METHOD: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society. RESULTS: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients). CONCLUSIONS: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately.

A Review of the Ultrasound Assessment of Diaphragmatic Function in Clinical Practice.

Ultrasonography is the only non-invasive, non-ionizing imaging technique widely available to directly assess diaphragmatic function. Two different sonographic approaches permit the assessment of muscle thickening in the zone of apposition and excursion of the dome of the diaphragm. Thanks to the new hand-held ultrasound instruments, the morphology and function of the diaphragm can be assessed in different settings, such as outpatient clinic, pulmonary function test laboratory, hospital department and intensive care unit, and under different conditions. Despite the existence of different acoustic views and several codified approaches, a comprehensive sonographic examination has never been standardized for clinical use. In this review, we summarize the clinical indications, methods and perspectives of the technique in adults.

Assessment of acute bronchodilator effects from specific airway resistance changes in stable COPD patients.

BACKGROUND: In COPD patients, reversibility is currently evaluated from the changes of forced expiratory volume at 1s (ΔFEV1) and forced vital capacity (ΔFVC). By lowering peripheral airway smooth muscle tone, bronchodilators should decrease dynamic hyperinflation, gas trapping, and possibly dyspnea at rest. Hence, we hypothesize that specific airway resistance changes (ΔsRAW) should better characterize the acute response to bronchodilators. METHODS: On two days, 60 COPD patients underwent dyspnea evaluation (VAS score) and pulmonary function testing at baseline and one hour after placebo or 300µg indacaterol administration. RESULTS: Spirographic and ΔsRAW-based criteria identified as responders 24 and 45 patients, respectively. ΔsRAW correlated with changes of intrathoracic gas volume (ΔITGV) (r=0.61; p<0.001), residual volume (ΔRV) (r=0.60; p<0.001), ΔFVC (r=0.44; p=0.001), and ΔVAS (r=0.73; p<0.001), while ΔFEV1 correlated only with ΔFVC (r=0.34; p=0.008). Significant differences in terms of ΔITGV (p=0.002), ΔRV (p=0.023), and ΔVAS (p<0.001) occurred only if patients were stratified according to ΔsRAW. CONCLUSIONS: In assessing the acute functional effect of bronchodilators, ΔsRAW-based criterion is preferable to FEV1-FVC-based criteria, being more closely related to bronchodilator-induced improvements of lung mechanics and dyspnea at rest.

Global alliance against chronic respiratory diseases in Italy (GARD-Italy): strategy and activities.

The steady increase in incidence of chronic respiratory disease (CRD) now constitutes a serious public health problem. CRDs are often underdiagnosed and many patients are not diagnosed until the CRD is too severe to prevent normal daily activities. The prevention of CRDs and reducing their social and individual impacts means modifying environmental and social factors and improving diagnosis and treatment. Prevention of risk factors (tobacco smoke, allergens, occupational agents, indoor/outdoor air pollution) will significantly impact on morbidity and mortality. The Italian Ministry of Health (MoH) has made respiratory disease prevention a top priority and is implementing a comprehensive strategy with policies against tobacco smoking, indoor/outdoor pollution, obesity, and communicable diseases. Presently these actions are not well coordinated. The Global Alliance against Chronic Respiratory Diseases (GARD), set up by the World Health Organization, envisages national bodies; the GARD initiative in Italy, launched 11/6/2009, represents a great opportunity for the MoH. Its main objective is to promote the development of a coordinated CRD program in Italy. Effective prevention implies setting up a health policy with the support of healthcare professionals and citizen associations at national, regional, and district levels. What is required is a true inter-institutional synergy: respiratory diseases prevention cannot and should not be the responsibility of doctors alone, but must involve politicians/policymakers, as well as the media, local institutions, and schools, etc. GARD could be a significant experience and a great opportunity for Italy to share the GARD vision of a world where all people can breathe freely.

Doppler echocardiographic assessment of the effects of inhaled long-acting beta2-agonists on pulmonary artery pressure in COPD patients.

Increase in pulmonary artery pressure (PAP), which is common in severe chronic obstructive pulmonary disease (COPD), is a predictor of mortality independent of airflow limitation. beta-agonists might slightly attenuate this increase because they exert a vasodilating effect on pulmonary circulation when systematically administered. We have investigated the acute effects of salmeterol and formoterol on echocardiographic systolic pulmonary artery pressure (sPAP) in 20 patients with COPD and a sPAP greater than 20mmHg at rest. Acute haemodynamic responses to inhaled formoterol or salmeterol were assessed in all patients, in a randomized, double-blind double-dummy fashion. On two consecutive days, patients received, in a randomized order, formoterol 12microg via Turbuhaler plus placebo via Diskus or salmeterol 50microg via Diskus plus placebo via Turbuhaler. Transthoracic Doppler echocardiography measurements of sPAP were made before and 15, 30, 60 and 180min after bronchodilator inhalation. Lung function, pulse oximetry and heart rate were also monitored at the same times. Mean sPAP significantly (p<0.05) decreased in comparison with baseline at 15, 30, and 60min post inhalation but returned towards control levels at 180min after both salmeterol and formoterol. There was no correlation between the maximum increase in FEV(1) and maximum decrease in sPAP either after inhalation of salmeterol (r(2)=0.071) or after that of formoterol (r(2)=0.0006). The increases in FEV(1) in comparison with baseline were always significant (p<0.05) from 15 to 180min post inhalation after either salmeterol or formoterol. Neither pulse oximetry nor heart rate changed in a significant manner (p>0.05). This study demonstrated that salmeterol and formoterol were equally beneficial for pulmonary haemodynamics in patients with COPD. A direct vasodilatation due to the activation of beta-adrenoceptors that are present in pulmonary vessels is a likely mechanism of their action in inducing the decrease in sPAP.