Mauro Carone

Quality standards for the management of bronchiectasis in Italy: A national audit

Although historically considered a neglected disease, bronchiectasis has become a disease of renewed interest over recent decades in light of an increase in prevalence and a substantial burden on healthcare systems [1–3]. In 2010, the British Thoracic Society (BTS) published guidelines on the management of bronchiectasis in adults, along with specific quality standards [4, 5]. To date, these represent the only quality standards available in Europe. These have been tested over a number of years in the UK with progressive improvements in the standard of care [6]. No national guidelines are available in Italy and no indications on which guideline should be followed have been given by the Italian Society of Respiratory Medicine (SIP). There are limited published data on the quality of bronchiectasis care in Europe outside of the UK. The BTS standards have not been tested in continental Europe or in Italy, where information on characteristics and management of bronchiectasis patients are lacking. The majority of the quality standards for the management of bronchiectasis in adults are not met in Italy http://ow.ly/YKMpU

Validity and reliability of a French version of the MRF-28 health-related quality of life questionnaire.

Background: Evaluation of health-related quality of life (HRQL) in chronic respiratory failure (CRF) is an important issue for evaluating the impact of treatment. Objectives: To elaborate a French version of the Maugeri Foundation Respiratory Failure Questionnaire (MRF-28) disease-specific HRQL questionnaire and determine its validity and reliability in patients with CRF treated by home mechanical ventilation (HMV). Methods: Forward- and back-translation of the MRF-28 questionnaire; the final version was submitted to 81 patients treated with HMV for CRF, simultaneously with the St. George’s Respiratory Questionnaire (SGRQ), the Short Form 36 (SF-36), and the Hospital Anxiety and Depression scale (HAD). Validity was determined by correlation with previously validated HRQL scores and recorded physiological parameters. Reliability was evaluated by assessing internal consistency and test-retest stability of the MRF-28 scores. Results: The French version of the MRF-28 and its subscores (‘daily activity’, ‘cognitive function’, and ‘invalidity’) were highly significantly correlated with subscores of the SGRQ, the SF-36 and the HAD. Both the MRF-28 and the SGRQ were correlated only with age and the 6-min walk test. The MRF-28 showed high test-retest reliability after 2 weeks (r2 = 0.80, p < 0.0001) and high internal consistency (Crohnbachs’ α coefficient: 0.91). Conclusion: The French version of the MRF-28 is a valid and reliable disease-specific questionnaire for assessing HRQL in patients with CRF.

Italian Registry of Patients with Alpha-1 Antitrypsin Deficiency: General Data and Quality of Life Evaluation

Abstract Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy. In a period spanning 18 years (1996–2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection.

Analysis of mitochondrial DNA alteration in new phenotype ACOS

BackgroundMitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD.MethodsTen (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR.ResultsACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47–137.0 ± 19.45–80.68 ± 4.16–92.69 ± 7.31 vs 65.97 ± 20.56).ConclusionWe found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.

Improvements in Lung Diffusion Capacity following Pulmonary Rehabilitation in COPD with and without Ventilation Inhomogeneity

Background: Lung diffusing capacity (D<smlcap>LCO</smlcap>) and lung volume distribution predict exercise performance and are altered in COPD patients. If pulmonary rehabilitation (PR) can modify D<smlcap>LCO</smlcap> parameters is unknown. Objectives: To investigate changes in D<smlcap>LCO</smlcap> and ventilation inhomogeneity following a PR program and their relation with functional outcomes in patients with COPD. Methods: This was a prospective, observational, multicentric study. Patients were evaluated before and after a standardized 3-week PR program. Functional assessment included body plethysmography, D<smlcap>LCO</smlcap>, transfer factor (KCO) and alveolar volume (V<smlcap>A</smlcap>), gas exchange, the 6-min walking test (6MWT) and exercise-related dyspnea. Patients were categorized according to the severity of airflow limitation and presence of ventilation inhomogeneity, identified by a V<smlcap>A</smlcap>/TLC <0.8. Results: Two hundred and fifty patients completed the study. Baseline forced expiratory volume in 1 s (FEV₁) % predicted (mean ± SD) was 50.5 ± 20.1 (76% males); 137 patients had a severe disease. General study population showed improvements in 6MWT (38 ± 55 m; p < 0.01), D<smlcap>LCO</smlcap> (0.12 ± 0.63 mmol × min^-1 kPa^-1; p < 0.01), lung function and dyspnea. Comparable improvements in D<smlcap>LCO</smlcap> were observed regardless of the severity of disease and the presence of ventilation inhomogeneity. While patients with V<smlcap>A</smlcap>/TLC <0.8 improved the D<smlcap>LCO</smlcap> increasing their V<smlcap>A</smlcap> (177 ± 69 ml; p < 0.01), patients with V<smlcap>A</smlcap>/TLC >0.8 improved their KCO (8.1 ± 2.8%; p = 0.019). The latter had also better baseline lung function and higher improvements in 6MWT (14.6 ± 6.7 vs. 9.0 ± 1.8%; p = 0.015). Lower D<smlcap>LCO</smlcap> at baseline was associated with lower improvements in 6MWT, the greatest difference being between subjects with very severe and mild D<smlcap>LCO</smlcap> impairment (2.7 ± 7.4 vs. 14 ± 2%; p = 0.049). Conclusions: In COPD patients undergoing a PR program, different pathophysiological mechanisms may drive improvements in D<smlcap>LCO</smlcap>, while ventilation inhomogeneity may limit improvements in exercise tolerance.

Health-related quality of life measurement in asthma and chronic obstructive pulmonary disease: review of the 2009-2014 literature

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are frequent in the general population. These diseases can worsen the quality of life of people suffering from them, limiting their daily activities and disrupting their sleep at night. Some questionnaires to measure the impact of the diseases on the daily life of patients are available. The measurements of subjective outcomes have become a part of clinical practice, and are used very frequently in clinical trials. Our aim was to describe how data on HRQoL in asthma and COPD are reported in papers published in the medical literature.MethodsWe identified papers on the recent respiratory drugs (chemical, not biological), that reported the HRQoL measurement and that were published from 2009 to April 2014. We planned to describe data about HRQoL, and we had no intention of comparing the degree of efficacy of drugs.ResultsThe most used questionnaires are the Asthma Quality of Life Questionnaire (AQLQ) and the Saint Georges Respiratory Questionnaire (SGRQ). These tools, administered at the baseline and at the end of the study (and interim evaluations in the longer studies) allowed for the identification of improvements as perceived by the patient after the treatment, even if in some cases these improvements were limited and not clinically relevant. Subjective measurements have always been placed among the secondary endpoints and the number of patients (estimated for the main endpoint) has often statistically overestimated the result. In addition, it is clear that subjective data is normally reported, but rarely commented on.ConclusionsThere are some methodology aspects that should be discussed in more depth, for example the necessity to express variations in the subjective perception, not as p-value but as effect-size.

Study of mitochondrial DNA alteration in the exhaled breath condensate of patients affected by obstructive lung diseases.

Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9  ±  4.9 versus 6.51  ±  0.21, p  <  0.05; 7.9  ±  2.5 versus 6.51  ±  0.21, p  =  0.06; 18.3  ±  3.4 versus 6.51  ±  0.21, p  <  0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.

Analysis of the fungal microbiome in exhaled breath condensate of patients with asthma

BACKGROUND The presence of virus and bacteria in the airways of subjects with asthma is common and seems to be associated with a deterioration due to the disease. The microbiologic study of airways in asthma is foreseen by guidelines with induced sputum that is often ineffective and contraindicated in severe asthma. AIM To analyze the fungal microbiome in the exhaled breath condensate (EBC) of subjects with asthma by evaluating a possible correlation with anthropometric and asthma severity data. METHODS We enrolled 47 consecutive subjects with asthma (28 with atopic asthma and 19 with nonatopic asthma) and 20 controls. Enrolled subjects underwent EBC and sputum collection. Fungal microbiome was assessed by culture on EBC and sputum samples by using Czapek yeast extract agar. RESULTS A fungal colonization in the EBC of 70% of enrolled subjects with asthma was detected (none detected in the controls). An overlap of fungal microbiome in EBC and sputum was observed (100% of overlap). Fungal colonization was higher in subjects without atopic, obesity, and severe and uncontrolled asthma. CONCLUSION When considering the high morbidity and mortality of patients with severe asthma in whom we found an important fungal airways colonization, we support the use of the analysis of exhaled fungal microbiome in these subjects.

Anxiety and depression in COPD

Chronic obstructive pulmonary disease (COPD) is a lung disease associated with chronic systemic inflammatory syndrome [1]. COPD is often associated with comorbidities that need to be evaluated because they affect the severity of the disease. Anxiety and depression are often observed in patients affected by COPD [2]. As pointed out by Tetikkurt and colleagues in this issue of Multidisciplinary Respiratory Medicine [3], COPD patients have to carry an important psychological burden related to their disease. In addition, in these patients, and due to unknown mechanisms, anxiety and depression increase the risk of re-hospitalization and increase mortality [4-6]. It is somewhat surprising that the degree of lung function impairment does not explain the level of anxiety and depression seen in these patients. Indeed, in most of the previous studies no correlation was found between the psychological aspects of COPD and the forced expiratory volume in 1 second (FEV1) value. Instead, anxiety or depression have been shown to be correlated to the presence of respiratory symptoms. Dyspnea and reduced exercise capacity are the predominant mechanisms leading to anxiety and depression symptoms associated with COPD. In the study by Tetikkurt and colleagues, the prevalence of these symptoms increased as the BODE index (a composite score of body mass, obstruction, dyspnea and exercise capacity) increased. The authors explain this finding arguing that dyspnea and reduced exercise capacity were the predominant mechanisms leading to the anxiety and depression associated with COPD. Indeed, dyspnea and reduced exercise capacity correlated significantly with the presence of the anxiety and depression symptoms. They conclude that the BODE index is superior to the Global Initiative for Obstructive Lung Disease (GOLD) classification for explaining anxiety and depression in COPD. Curiously, also bronchoalveolar lavage (BAL) cytologic findings correlated significantly with the presence of the anxiety and depression symptoms. Tetikkurt and colleagues explain this finding by reasoning that BAL abnormalities reflect the distal lung damage, and as the lung damage gets worse dys pnea increases. Indeed, the correlation found between the severity of the atypical findings of BAL cytology and the Modified Medical Research Council (MMRC) index and the 6-minute walk distance (6 MWD) suggests that dyspnea and the consequent functional physical limitation may be related to the severity of the peripheral lung damage identified by BAL cytology. Tetikkurt and colleagues may go a bit too far in suggesting BAL cytology as a screening tool for COPD patients to determine the presence of symptoms of anxiety or depression, or as a noninvasive tool for identifying psychiatric comorbidities. However, the results are very interesting and worth further investigating. In conclusion, anxiety and depression are common symptoms in COPD. There is a clear association between dyspnea and anxiety or depression in COPD, and these symptoms are correlated with and contribute to the severity of the disease. Further studies are needed to better understand the relationship between psychological abnormalities and the pathophysiology of COPD.

Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with high pathological burden and healthcare costs [1–3]. In outpatient clinical practice, an accurate differential diagnosis is often very difficult, particularly in adult smokers, requiring specific lung function tests [4, 5]. Since nuclear magnetic resonance (NMR)-based metabolomics of exhaled breath condensate (EBC) discriminates adults with COPD [6–8] or asthma [9] from healthy subjects, we hypothesised that it is also able to differentiate asthma and COPD patients of different severities. NMR profiling of EBC discriminates between asthma and COPD and this may help clinicians with differential diagnosis http://ow.ly/cNGI30hWYAE