TRITRIAL: The Impact of Fixed Triple Therapy with Beclometasone/Formoterol/Glycopyrronium on Health Status and Adherence in Chronic Obstructive Pulmonary Disease in an Italian Context of Real Life.

Purpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient's experience and perspective through the use of patients reported outcomes. Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes. Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5-0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the study. Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients' HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.

Comparing the Effectiveness, Tolerability, and Acceptability of Heated Tobacco Products and Refillable Electronic Cigarettes for Cigarette Substitution (CEASEFIRE): Randomized Controlled Trial.

BACKGROUND: People who smoke and who face challenges trying to quit or wish to continue to smoke may benefit by switching from traditional cigarettes to noncombustible nicotine delivery alternatives, such as heated tobacco products (HTPs) and electronic cigarettes (ECs). HTPs and ECs are being increasingly used to quit smoking, but there are limited data about their effectiveness. OBJECTIVE: We conducted the first randomized controlled trial comparing quit rates between HTPs and ECs among people who smoke and do not intend to quit. METHODS: We conducted a 12-week randomized noninferiority switching trial to compare effectiveness, tolerability, and product satisfaction between HTPs (IQOS 2.4 Plus) and refillable ECs (JustFog Q16) among people who do not intend to quit. The cessation intervention included motivational counseling. The primary endpoint of the study was the carbon monoxide-confirmed continuous abstinence rate from week 4 to week 12 (CAR weeks 4-12). The secondary endpoints included the continuous self-reported ≥50% reduction in cigarette consumption rate (continuous reduction rate) from week 4 to week 12 (CRR weeks 4-12) and 7-day point prevalence of smoking abstinence. RESULTS: A total of 211 participants completed the study. High quit rates (CAR weeks 4-12) of 39.1% (43/110) and 30.8% (33/107) were observed for IQOS-HTP and JustFog-EC, respectively. The between-group difference for the CAR weeks 4-12 was not significant (P=.20). The CRR weeks 4-12 values for IQOS-HTP and JustFog-EC were 46.4% (51/110) and 39.3% (42/107), respectively, and the between-group difference was not significant (P=.24). At week 12, the 7-day point prevalence of smoking abstinence values for IQOS-HTP and JustFog-EC were 54.5% (60/110) and 41.1% (44/107), respectively. The most frequent adverse events were cough and reduced physical fitness. Both study products elicited a moderately pleasant user experience, and the between-group difference was not significant. A clinically relevant improvement in exercise tolerance was observed after switching to the combustion-free products under investigation. Risk perception for conventional cigarettes was consistently higher than that for the combustion-free study products under investigation. CONCLUSIONS: Switching to HTPs elicited a marked reduction in cigarette consumption among people who smoke and do not intend to quit, which was comparable to refillable ECs. User experience and risk perception were similar between the HTPs and ECs under investigation. HTPs may be a useful addition to the arsenal of reduced-risk alternatives for tobacco cigarettes and may contribute to smoking cessation. However, longer follow-up studies are required to confirm significant and prolonged abstinence from smoking and to determine whether our results can be generalized outside smoking cessation services offering high levels of support. TRIAL REGISTRATION: ClinicalTrials.gov NCT03569748; https://clinicaltrials.gov/ct2/show/NCT03569748.

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey.

INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. METHODS: We designed a survey (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), assessing several symptoms that have been associated with Long-COVID to be administered nationwide to COVID-19 survivors; the survey also included effort perception, measured using the Borg scale. Patients receiving the survey were divided in two groups, with a 2:1 ratio: the first group included patients that received L-Arginine + Vitamin C, whereas the second group received a multivitamin combination (alternative treatment). RESULTS: 1390 patients successfully completed the survey. Following a 30-day treatment in both groups, the survey revealed that patients in the L-Arginine + Vitamin C treatment arm had significantly lower scores compared to patients who had received the multivitamin combination. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p < 0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm. CONCLUSIONS: Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception.

Narrative Analysis of the Impact of COVID-19 on Patients with Chronic Obstructive Pulmonary Disease, Their Caregivers, and Healthcare Professionals in Italy.

Purpose: The COVID-19 pandemic has disrupted many lives, including those of people suffering from chronic obstructive pulmonary disease (COPD) and their caregivers. The main aim of this study was to use narrative medicine, a validated approach promoting quality of care to explore how the COVID-19 pandemic impacted the quality of care, quality of life, psychological factors and social factors of people affected by COPD and their caregivers and healthcare professionals (HCPs). A secondary aim was to explore the role of telemedicine in combating isolation and providing access to care. Methods: A cross-sectional observational narrative medicine study was conducted between July and November 2020 across Italy. An online semi-structured questionnaire with a narrative plot was completed by 146 participants (79 COPD patients, 24 caregivers, and 43 HCPs). Narrations were analyzed with descriptive statistics and evaluated using NVivo 11 software to break down the text and identify recurring themes and major semantic clusters. Results: During the first lockdown, 58.22% of responses from COPD patients indicated terror, fear and/or apprehension; at reopening, this figure was 35.44%. Among caregivers, these figures were 100% at first lockdown and 45.83% at reopening. The metaphors most commonly used by patients to describe COPD and COVID-19 were monster and murderer, respectively. Patients described their homes more often as clean and lonely than as offering no shelter. The narratives of 42 COPD patients (45.2%) described coping. Only 12.6% of COPD patients reported regular access to medical visits during lockdown, while 59.1% of general practitioners and pulmonologists reported using telemedicine, which was perceived as satisfactory by both patients and caregivers. Conclusion: It is relevant to aim for a multidisciplinary and multilevel system of care that empowers telemedicine and integrates specific psychological support programs for COPD patients and their caregivers.

Health outcomes in COPD smokers using heated tobacco products: a 3-year follow-up.

Given that many patients with chronic obstructive pulmonary disease (COPD) smoke despite their symptoms, it is important to understand the long-term health impact of cigarette substitution with heated tobacco products (HTPs). We monitored health parameters for 3 years in COPD patients who substantially attenuated or ceased cigarette consumption after switching to HTPs. Changes in daily cigarette smoking, annualized disease exacerbations, lung function indices, patient-reported outcomes (CAT scores) and 6-minute walk distance (6MWD) from baseline were measured in COPD patients using HTPs at 12, 24 and 36 months. These were compared to a group of age- and sex-matched COPD patients who continued smoking. Complete data sets were available for 38 patients (19 in each group). Subjects using HTPs had a substantial decrease in annualized COPD exacerbations within the group mean (± SD) from 2.1 (± 0.9) at baseline to 1.4 (± 0.8), 1.2 (± 0.8) and 1.3 (± 0.8) at 12-, 24- and 36-month follow-up (p < 0.05 for all visits). In addition, substantial and clinically significant improvements in CAT scores and 6MWD were identified at all three time points in the HTP cohort. No significant changes were observed in COPD patients who continued smoking. This study is the first to describe the long-term health effects of HTP use in COPD patients. Consistent improvements in respiratory symptoms, exercise tolerance, quality of life, and rate of disease exacerbations were observed in patients with COPD who abstained from smoking or substantially reduced their cigarette consumption by switching to HTP use.

COPD smokers who switched to e-cigarettes: health outcomes at 5-year follow up.

BACKGROUND AND AIMS: The long-term health effects of the use of electronic cigarettes (ECs) in patients with chronic obstructive pulmonary disease (COPD) are largely unexplored. We present findings from a 5-year prospective assessment of respiratory parameters in a cohort of COPD patients who substantially reduced conventional smoking or achieved abstinence by switching to ECs. METHODS: Patients were evaluated prospectively for their measurements of respiratory exacerbations, spirometric indices, quality of life using the COPD assessment tool (CAT), 6-min walk distance (6MWD), as well as conventional cigarette consumption. Baseline measurements prior to switching to EC use were compared with follow-up visits at 12-, 24-, 48- and 60-months. Age- and sex-matched COPD patients reporting to be regular smokers (not using ECs) were the reference group for the analysis. RESULTS: Complete data were available from 39 patients. Those in the EC user group achieved a marked decline in cigarette smoking or abstinence. COPD EC users had a significant diminution in COPD exacerbations; with the mean (±SD) exacerbation rate falling from 2.3 (±0.9) at baseline to 1.1 (±1.0) at 5 years (p < 0.001), whereas no significant changes were observed in the control group.Significant and constant improvements in lung function, CAT scores and 6MWD were reported in the EC user group over the 5-year observation period compared with the reference group (p < 0.05). CONCLUSION: The present study suggests that EC use may ameliorate objective and subjective COPD outcomes, and that the benefits gained appear to persist long term. EC use for abstinence and smoking reduction may ameliorate some of the harm resulting from tobacco smoking in COPD patients.

Physical Functioning in Patients with Chronic Obstructive Pulmonary Disease Treated with Tiotropium/Olodaterol Respimat in Routine Clinical Practice in Italy.

INTRODUCTION: Clinical studies have shown significant improvements in exercise capacity in patients with chronic obstructive pulmonary disease (COPD) who are treated with a tiotropium/olodaterol fixed-dose combination (FDC). However, the effects of this treatment, which is administered in a single device, on physical functioning in a real-life setting of patients with COPD had not been fully determined. METHODS: An open-label, observational study was conducted in 309 patients with COPD from 29 sites across Italy who received tiotropium/olodaterol FDC for 6 weeks. Physical functioning was evaluated using the Physical Functioning Questionnaire (PF-10). The primary endpoint was the proportion of patients with therapeutic success, defined as a ten-point increase in the PF-10 score from the baseline visit. Secondary endpoints were absolute changes in PF-10 score from baseline visit, the patient's general condition assessed by the Physician's Global Evaluation (PGE) score, and patient satisfaction with treatment, inhaling and handling of the device. RESULTS: According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) multimodality assessment, most patients were allocated to groups B (44.4%) and D (24.5%). Comorbidities were present in 73.9% of the patients. The primary endpoint was reached in more than half of the patients (52.5%), especially in groups B and D of GOLD. Patients' satisfaction with treatment, inhaling and handling of device was high, with a range of more than 86% to more than 89%, and very high in both groups B and D. The rates of drug-related adverse events were very low. CONCLUSIONS: This real-life study showed that the tiotropium/olodaterol FDC treatment delivered via the Respimat device improves physical functioning and general patients' condition and is associated with a high degree of satisfaction and very low rates of drug-related adverse events, regardless of the group they belong to and their comorbidities. CLINICAL TRIAL ID: NCT03003494.

Successful Extracorporeal Membrane Oxygenation Treatment in an Acquired Immune Deficiency Syndrome (AIDS) Patient with Acute Respiratory Distress Syndrome (ARDS) Complicating Pneumocystis jirovecii Pneumonia: A Challenging Case.

BACKGROUND Patients with HIV infection tend to have poor intensive care unit (ICU) outcomes; however, survival in the modern combination antiretroviral therapy (cART) era has markedly improved, but Pneumocystis jirovecii pneumonia (PJP) still remains a preeminent cause of respiratory failure in AIDS patients. Extracorporeal membrane oxygenation (ECMO) is an adapted cardiopulmonary bypass circuit for temporary life support for patients not responding to conventional treatment. CASE REPORT A 43-year-old male HIV "late presenter" was admitted to our hospital for fever and dyspnea. A chest CT scan revealed bilateral ground-glass opacities. Empiric antibiotic treatment and cART were started. The emergence of ARDS due to PJP dictated urgent veno-venous (VV) ECMO placement. One week later, radiologic findings and respiratory function had improved and the patient was started on a weaning trial from ECMO and removed 12 days after placement. CONCLUSIONS Acute respiratory distress syndrome (ARDS) is a potentially reversible clinical syndrome with a high mortality rate. ECMO is a rescue therapy allowing lung recovery during acute processes and should be considered an adequate treatment option in HIV+ patients with respiratory failure. ECMO should be considered a useful and adequate treatment option in AIDS patients who have a high risk of dying from respiratory failure.

Non-inferiority trial comparing cigarette consumption, adoption rates, acceptability, tolerability, and tobacco harm reduction potential in smokers switching to Heated Tobacco Products or electronic cigarettes: Study protocol for a randomized controlled trial.

BACKGROUND: Despite the introduction of tobacco control measures, smoking remains highly prevalent in most EU countries. In Italy, one in four adults were still regular smokers in 2017. Increasing use of combustion-free delivering nicotine technologies for cigarette substitution may accelerate the current downward trends in smoking prevalence. Whether Heated Tobacco Products (HTPs) are more effective tobacco smoking substitutes that may potentially facilitate adoption and full conversion compared to e-cigarettes (ECs) is not known.We have designed a prospective study to compare changes in cigarette consumption and adoption rates among smokers randomized to either HTPs or ECs. Product acceptability, tolerability, and their tobacco harm reduction potential will be also compared. METHODS: 220 healthy smokers, not motivated to quit, will be randomized into a 12-weeks single-center, open label, non-inferiority trial comparing study outcomes from HTPs vs. ECs use. The primary outcome will be biochemically verified self-reported continuous abstinence at 12-weeks from the previous visit. Secondary outcomes will include: smoking reduction from baseline, adoption rates and product acceptability, tolerability, changes in step test values and in the level of selected biomarkers of exposure in exhaled breath (i.e. eCO) and in spot urine samples. A follow-up visit will be also included at 24-weeks to review product usage and smoking behavior under naturalistic condition of use.Recruitment of participants started in May 2019 and enrolment is expected to be completed in November 2019. DISCUSSION: This will be the first study directly comparing Heated Tobacco Products with Electronic Cigarettes in term of reduction in cigarette consumption, adoption rates, product acceptability, tolerability, and tobacco harm reduction potential. This knowledge can contribute to a better understanding of the potential role of this new technology in the evolving nicotine consumer market. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03569748.Registered June 25, 2018.https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4.

Efficacy of osteopathic treatment in patients with stable moderate-to-severe chronic obstructive pulmonary disease: a randomized controlled pilot study.

Background This randomized controlled pilot study evaluated the efficacy of osteopathic treatment in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) assessed using spirometry, COPD Assessment Test (CAT) and six minutes walking test (6MWT). The main goals were to improve the quality of life of patients with stable moderate-to-severe COPD, and to revise the parameters of the assessment tests, such as spirometry and 6MWT. Methods The study comprised several phases and patients were divided into two groups: group A (controls) received conventional pharmacological treatment with Indacaterol-Glycopyrronium and, while group B (OMT group) received both traditional therapy and osteopathic manipulative treatment (OMT) at different stages of the study. The osteopathic approach focused on maxillary sinus, vertebral-pleural ligaments, phrenic nerves, ribs, pleura, lungs, bronchi, subclavian muscles, and trapezoid and conoid ligaments. Results Overall, 32 patients were randomized and treated. Patients of the OMT group got better improvements in all tests compared to the control group: spirometry: FVC (p<0.5411), total FEV1 (p<0.5061); CAT: OMT (p<0.0005) - controls (p<0.188) 6MWT OMT (p<0.0038) - controls (p<0.5326). The clinical results collected in phase (T3) confirm those obtained in the first sessions; the results of CAT questionnaire (p<0.0005) and 6MWT (p

Health effects in COPD smokers who switch to electronic cigarettes: a retrospective-prospective 3-year follow-up.

Background: Health effects of electronic cigarette (EC) use in patients with chronic obstructive pulmonary disease (COPD) are largely unexplored. Aim: We present findings from a long-term prospective assessment of respiratory parameters in a cohort of COPD patients who ceased or substantially reduced conventional cigarette use with ECs. Methods: We prospectively re-evaluated COPD exacerbations, spirometric indices, subjective assessments (using the COPD Assessment Tool [CAT] scores), physical activity (measured by the 6-minute walk distance [6MWD]), and conventional cigarette use in EC users with COPD who were retrospectively assessed previously. Baseline measurements prior to switching to EC use were compared to follow-up visits at 12, 24, and 36 months. Age- and sex-matched regularly smoking COPD patients who were not using ECs were included as reference (control) group. Results: Complete data were available from 44 patients. Compared to baseline in the EC-user group, there was a marked decline in the use of conventional cigarettes. Although there was no change in lung function, significant improvements in COPD exacerbation rates, CAT scores, and 6MWD were observed consistently in the EC user group over the 3-year period (p<0.01). Similar findings were noted in COPD EC users who also smoked conventional cigarettes ("dual users"). Conclusion: The present study suggests that EC use may ameliorate objective and subjective COPD outcomes and that the benefits gained may persist long-term. EC use may reverse some of the harm resulting from tobacco smoking in COPD patients.

Pharmacological approach and adherence to treatment recommendations in frequently and non-frequently exacerbating COPD patients from Italy: MISTRAL - The prospective cohort, observational study.

BACKGROUND: Several documents and guidelines provide recommendations for effective management of COPD patients. However, there is often a significant imbalance between recommended treatment of COPD patients and the actual care provided both in primary care and specialty setting. This imbalance could result in a significant negative impact on patients' health status and quality of life, leading to increased hospitalisations and health resource utilisation in COPD patients METHODS: MISTRAL was an observational, longitudinal, prospective cohort study, designed to assess the overall pharmacological approach of COPD in routine clinical practice in Italy. Eligible patients were divided into two cohorts based on their exacerbation history in the year prior to the enrolment, frequent exacerbators (FEs; ≥2 exacerbations), and non-frequent exacerbators (NFEs; ≤1 exacerbation). The primary objective was to assess adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 treatment recommendations in FEs and NFEs at baseline and follow-up visits RESULTS: Of the 1489 enrolled patients, 1468 (98.6%; FEs, 526; NFEs, 942) were considered evaluable for analyses. At baseline, 57.8% of patients were treated according to GOLD 2011 recommendations; a greater proportion of FEs were treated according to GOLD recommendations, compared with NFEs patients at baseline (77.1% versus 46.7%; P < 0.0001), and all study visits. At baseline, GOLD group D patients were the most adherent (81.2%) to treatment recommendations, while group A patients were the least adherent (30.3%) at baseline, attributed mainly to overuse of inhaled corticosteroids in less severe GOLD groups. Triple therapy with long-acting muscarinic antagonist (LAMA) + long-acting ß2-agonist/inhaled corticosteroid (LABA/ICS) was the most frequent prescribed treatment at all study visits, irrespective of patient's exacerbation history. Changes in treatment were more frequent in FEs versus NFEs CONCLUSIONS: The Mistral study reports a scarce adherence to the GOLD 2011 treatment recommendations in routine clinical practice in Italy. The adherence was particularly low in less severe, non-frequent exacerbating patients mostly for ICS overuse, and was higher in high-risk, frequent exacerbating COPD patients.

Evidence for harm reduction in COPD smokers who switch to electronic cigarettes.

BACKGROUND: Electronic cigarettes (ECs) are battery-operated devices designed to vaporise nicotine, which may help smokers quitting or reducing their tobacco consumption. There is a lack of data on the health effects of EC use among smokers with COPD and whether regular use results in improvement in subjective and objective COPD outcomes. We investigated long-term changes in objective and subjective respiratory outcomes in smokers with a diagnosis of COPD who quit or reduced substantially their tobacco consumption by supplementing with or converting only to ECs use. METHODS: We conducted a retrospective chart review of patients with COPD to identify those reporting regular daily use of ECs on at least two follow-up visits at 12- (F/up1) and 24-months (F/up2). Regularly smoking COPD patients were included as a reference group. RESULTS: A marked reduction in cigarette consumption was observed in ECs users. A significant reduction in COPD exacerbations was reported in the COPD EC user group, their mean (±SD) decreasing from 2.3 (±1) at baseline to 1.8 (±1; p = 0.002) and 1.4 (±0.9; p < 0.001) at F/up1 and F/up2 respectively. A significant reduction in COPD exacerbations was also observed in ECs users who also smoked conventional cigarettes (i.e. 'dual users'). COPD symptoms and ability to perform physical activities improved statistically in the EC group at both visits, with no change in the control group. CONCLUSIONS: These findings suggest that ECs use may aid smokers with COPD reduce their cigarette consumption or remain abstinent, which results in marked improvements in annual exacerbation rate as well as subjective and objective COPD outcomes.

Linking MRI hyperintensities with patterns of neuropsychological impairment: evidence for a threshold effect.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) might interrupt intra- and interhemispheric communication and thus induce cognitive impairments and dementia. It remains unclear, however, if there is a volume threshold of LA that is needed before either the signs of dementia and/or a specific pattern of neuropsychological impairment become manifest. Roman et al has suggested that 25% of white matter may need to be involved before white matter alterations influence the clinical signs associated with dementia. The purpose of this study is to ascertain the threshold of MRI-LA as measured with a visual rating scale needed to induce specific patterns of neuropsychological impairment associated with dementia. METHODS: One hundred fifteen patients with dementia received a comprehensive neuropsychological examination and the severity of MRI-LA was measured using a 40-point LA scale. RESULTS: Patients were categorized into low (mean LA=4.21+/-2.92; 3.22%-17.82%), moderate (mean LA=12.58+/-2.54; 25.01%-37.80%), and severe (mean LA=22.36+/-4.04; 45.80%-66.00%) LA groups. Patients in the mild LA group obtained markedly lower scores on tests of episodic memory compared with working memory, a neuropsychological profile often associated with Alzheimer disease. Patients with moderate LA displayed equal impairment on neuropsychological tests. Patients in the severe LA group obtained significantly lower scores on tests of working memory as compared with episodic memory. CONCLUSIONS: These data provide evidence that a threshold of moderate MRI-LA as measured with a visual rating scale is associated with greater and/or equal impairment on tests of working memory versus episodic memory and provides a benchmark to assess the effect of MRI-LA on the clinical presentation of dementia.