Il significato clinico dell'ossido nitrico nell'asma

Bronchial asthma is an inflammatory disease and measurement of biomarkers in exhaled breath has recently become an attractive approach to non-invasively monitor airway inflammation. In bronchial asthma, increased fractional exhaled nitric oxide (FeNO) concentration in exhaled breath has been shown to reflect the extent of eosinophilic inflammation. Moreover, the increase of FeNO levels are suppressed by inhaled corticosteroids (ICS). Therefore, monitoring of FeNO is a useful marker of inflammation in asthma and it has proven to be very effective in the differential diagnosis of allergic asthma, predicting the response to ICS therapy. Several FeNO analyzers are commercially available. Because of great advances in technology a wide range of hand-held FeNO analyzers and smaller less costly devices are now becoming available, making FeNO measurement a routine test in the primary care of asthmatic patients. In the first study we tested a new portable device to investigate correlation and agreement with the standard stationary device. Nowadays, overweight and obesity are common conditions worldwide. In particular, the incidence of overweight and obesity in Italian people is estimated almost of 32% and 10%, respectively. Obesity has been considered as a proinflammatory state and therefore several studies have been investigated the relationship between elevated body mass index (BMI) and asthma. In the second study we aimed to investigate in a large cohort of Italian asthmatic patients whether or not overweight patients were different from normal weight subjects both in terms of clinical and functional features and in terms of airway inflammation, as assessed by FeNO measurement. Although the clinical application of FeNO is still needed to be fully clarified, the use of this marker in clinical practice is providing a useful adjunct to conventional tools for the assessment and management of the respiratory disease. There is a general agreement that the development of new techniques detecting the distinct patterns of biomarkers in exhaled breath heralds the beginning of the era of “Breathomics”. In this regard, future developments may include FeNO “breathograms” to aid early detection, diagnosis and follow-up of airways diseases.L’asma bronchiale è una patologia infiammatoria cronica delle vie aeree. Negli ultimi anni, la misurazione di biomarkers nell’aria esalata è diventata una metodica non invasiva di uso comune per la valutazione dell’infiammazione delle vie aeree. Nell’asma bronchiale, è stato dimostrato che valori elevati della frazione dell’ossido nitrico esalato (FeNO) riflettono il grado di infiammazione eosinofilica delle vie aeree. Inoltre, il trattamento con corticosteroidi inalatori (ICS) riduce i valori di FeNO. Di conseguenza, la misurazione del FeNO è un utile biomarker dell’infiammazione nell’asma ed è stato validato come parametro molto utile nella diagnosi differenziale dell’asma allergica in quanto predice la risposta al trattamento con ICS. Attualmente in commercio sono disponibili diversi analizzatori del FeNO. Grazie al progresso della tecnologia sta diventando disponibile una grande varietà di analizzatori portatili, più piccoli e meno costosi, il che rende la misurazione del FeNO un test di routine nella pratica clinica dell’asma. Nel primo studio abbiamo testato un nuovo apparecchio portatile per valutarne la correlazione e la concordanza con l’apparecchio stanziale standard. Attualmente, sovrappeso e obesità sono condizioni molto diffuse. Nello specifico, nella popolazione italiana l’incidenza di sovrappeso e obesità è di circa 32% e 10%, rispettivamente. L’obesità è considerata come uno stato pro-infiammatorio, pertanto diversi studi hanno approfondito la relazione tra elevato indice di massa corporea (Body Mass Index, BMI) e asma. Nel secondo studio ci siamo posti l’obiettivo di verificare se, in un’ampia coorte di pazienti asmatici italiani, i pazienti in sovrappeso differivano dai soggetti normopeso in termini di aspetti clinico-funzionali e di infiammazione delle vie aeree stimata con la misurazione del FeNO. Sebbene le applicazioni cliniche del FeNO non siano ancora completamente validate, l’utilizzo di questo marker nella pratica clinica fornisce un valore aggiuntivo agli strumenti convenzionali nella valutazione ed il monitoraggio delle malattie respiratorie. C’è un consenso generale riguardo al fatto che lo sviluppo di nuove tecniche in grado di determinare i differenti patterns dei biomarkers nell’esalato segna l’inizio dell’era della “Breathomics”. A questo riguardo, futuri sviluppi potrebbero includere i “breathograms” del FeNO come metodica di supporto nella diagnosi precoce e nel follow-up delle malattie delle vie aeree

The COPD assessment test and the modified Medical Research Council scale are not equivalent when related to the maximal exercise capacity in COPD patients.

INTRODUCTION The management and treatment of Chronic Obstructive Pulmonary Disease (COPD) are based on a cutoff point either of ≥ 10 on the COPD Assessment Test (CAT) or of ≥ 2 of the Medical Research Council (mMRC). Up to now, no study has assessed the equivalence between CAT and mMRC, as related to exercise tolerance in COPD. The aim of this study was to investigate as primary outcome the relationship between CAT and mMRC and maximal exercise capacity in COPD patients. We also evaluated as secondary outcome the agreement between CAT (≥ 10) and mMRC (≥ 2) to categorize patients according to their exercise tolerance. MATERIAL AND METHODS 118 consecutive COPD patients (39 females), aged between 47 and 85 years with a wide range of airflow obstruction and lung hyperinflation were studied. Maximal exercise capacity was assessed by cardiopulmonary exercise test. RESULTS CAT and mMRC scores were significantly related to VO2 peak (p<0.01). CAT (≥ 10) and mMRC (≥ 2) have a high likelihood to be associated to a value of VO2 peak less than 15.7 and 15.6 mL/kg/min, respectively. The interrater agreement between CAT (≥ 10) and mMRC (≥ 2) was found to be fair (κ = 0.20) in all patients but slight when they were subdivided in those with VO2 peak < 15 mL/kg/min and in those with VO2 peak ≥ 15 mL/kg/min (κ = 0.10 and κ = 0.20 respectively). CONCLUSION This study shows that CAT and mMRC are useful tools to predict exercise tolerance in COPD, but they cannot be considered as supplementary measures

Arachidonic acid and docosahexaenoic acid metabolites in the airways of adults with cystic fibrosis: effect of docosahexaenoic acid supplementation.

Cystic fibrosis (CF) is an autosomal recessive disorder, caused by genetic mutations in CF transmembrane conductance regulator (CFTR) protein. Several reports have indicated the presence of specific fatty acid alterations in CF patients, most notably decreased levels of plasmatic and tissue docosahexaenoic acid (DHA), the precursor of Specialized Pro-resolving Mediators (SPMs). We hypothesized that DHA supplementation could restore the production of DHA-derived products and possibly contribute to a better control of the chronic pulmonary inflammation observed in CF subjects. Sputum samples from 15 CF and 10 Chronic Obstructive Pulmonary Disease (COPD) subjects were collected and analyzed by LC/MS/MS and blood fatty acid were profiled by gas chromatography upon lipid extraction and transmethylation. As compared to COPD patients, CF subjects showed increased concentrations of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and 15-hydroxyeicosatetraenoic acid (15-HETE), while the concentrations of DHA metabolites were not different in the two groups. After DHA supplementation, not only DHA/AA ratio and highly unsaturated fatty acid (HUFA) index were significantly increased (p &lt; 0.05), but CF subjects showed a tendency toward a decrease in LTB4 and PGE2 and an increase in 17-hydroxy-docosahexaenoic acid (17OH-DHA) levels, together with a significantly reduction in 15-HETE. At the end of the washout period, LTB4, PGE2, 15-HETE, and 17OH-DHA tended to recover baseline values. As compared to baseline, 15-HETE/17OH-DHA ratio significantly changed after supplementation (p &lt; 0.01). Our results showed that in CF patients an impairment in fatty acid metabolism, characterized by increase in AA metabolites and decrease in DHA, was partially corrected by DHA supplementation

Small airway dysfunction predicts excess ventilation and dynamic hyperinflation during exercise in patients with COPD

Introduction: Small airway dysfunction (SAD) is a pathophysiological characteristic of chronic obstructive pulmonary disease (COPD). Excess ventilation and dynamic hyperinflation (DH) are two main pathophysiological traits and limiting factors of COPD patients while exercising. We aimed to ascertain whether or not SAD, assessed by the multiple breath nitrogen washout (MBNW), may predict exercise ventilatory inefficiency and DH. Methods: Fifty stable COPD patients were prospectively studied and underwent MBNW and incremental cardio-pulmonary exercise test (CPET). Indices of conductive (Scond) and acinar (Sacin) ventilation heterogeneity as well as minute ventilation/CO2 production (VE/VCO2) linear relationship and the change in inspiratory capacity (IC) were analyzed. Results: Sacin was significantly and directly related to VE/VCO2 slope and inversely related to IC change and to peak O2 uptake (p < 0.01 for all correlations). No significant correlation was found between Scond and CPET parameters. The regression equation generated by stepwise multiple regression analysis for the VE/VCO2 slope and IC change, as dependent variables, included only Sacin, as independent variable. This model accounted for 31% and 36% of the total variance for the VE/VCO2 slope and IC change, respectively. Conclusion: Our study shows the value of the SAD as determinant of the excess ventilation and DH during exercise in patients with stable COPD

SEM Investigation about Hyphal Relationships between Some Antagonistic Fungi against «Fusarium» spp. Foot Rot Pathogen of Wheat

Wheat foot rot caused by Fusarium species is a worldwide wheat disease against which the use of biocontrol agents is of increasing interest. Mycoparasitic activities of a strain of five antagonistic fungi, Gliocladium roseum (GR11), Penicillium frequentans (PF), Trichoderma atroviride (TA312), T. longibrachiatum (TL9) and T. harzianum (TH144), against three pathogens, Fusarium culmorum, F. graminearum and F. nivale, were studied by scanning electron microscopy (SEM). SEM observations suggested that the outcome of interaction between antagonist and pathogen occurred when intimate contact was established between hyphae triggering a series of events in pathogen degradation. The interaction between Trichoderma spp. and Fusarium spp. revealed that the mycoparasitic hyphae were usually attached longitudinally to the hyphae of the pathogens; hyphal coilings, hooks, pincer-shaped structures, short contact branches and hyphal depressions were also present. GR11 and PF hyphae grew mainly parallel to the pathogen causing its hyphal depression. The parasitic action of the antagonists shown with the formation of pincers, hooks and other structures leading to cell disruption, goes some way towards explaining their mode of action in the biological control of the pathogens studied

Pleural tuberculosis: medical thoracoscopy greatly increases the diagnostic accuracy

Our objective was to evaluate the efficacy of a standardised work-up in the diagnosis of pleural tuberculosis (TB) that included fibreoptic bronchoscopy and medical thoracoscopy. A consecutive series of 52 pleural TB patients observed during the period 2001-2015 was evaluated retrospectively. 20 females, mean (range) age 39.7 (18-74) years, and 32 males, mean (range) age 45.75 (21-83) years, were included (28 non-EU citizens (53.8%)). The diagnosis of TB infections was established by identification (using stains, culture or molecular tests) of Mycobacterium tuberculosis in the pleura, sputum and/or bronchial specimens, or by evidence of caseous granulomas on pleural biopsies. Patients with and without lung lesions were considered separately. The diagnostic yield of the microbiological tests on pleural fluid was 17.3% (nine out of 52 patients). Among the 18 patients with lung lesions, bronchial samples (washing, lavage or biopsy) were positive in 50% of cases (nine patients). Cultures of pleural biopsies were positive in 63% of cases (29 out of 46 patients); pleural histology was relevant in all patients. Without pleural biopsy, a diagnosis would have been reached in 15 out of 52 patients (28.6%) and in four of them only following culture at 30-40 days. An integrated diagnostic work-up that includes all the diagnostic methods of interventional pulmonology is required for a diagnosis of pleural TB. In the majority of patients, a diagnosis can be reached only with pleural biopsy

Beclomethasone/Formoterol in Extra-Fine Formulation Improves Small Airway Dysfunction in COPD Patients

INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), small airway dysfunction (SAD) is a key element and a functional consequence of the pathology. The exact role of SAD as a specific 'pharmacological target' represents an important research topic. Our objective was to ascertain whether an extra-fine formulation of beclomethasone dipropionate/formoterol fumarate (BDP/FF) NEXThaler 100/6mug b.i.d. could improve SAD and, consequently, the quality of life of COPD patients.METHODS: We enrolled COPD patients with severe airflow obstruction and at least one moderate exacerbation in the previous year, having started treatment with BDP/FF NEXThaler for no more than 1 week. Patients underwent three visits: at the start of the treatment (V1), 6 weeks (V2), and 12weeks later (V3). At each visit, we evaluated the fall in resistance from 5 to 20Hz (R5-R20) and residual volume/total lung capacity (RV/TLC) ratio by impulse oscillometry, spirometry, and plethysmography. The COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also administered to assess the disease's impact on quality of life.RESULTS: We enrolled 43 COPD patients (mean age 69years, FEV1 43%). R5-R20 significantly changed from baseline [0.23±0.09kPa/(l/s)] to V2 [0.16±0.09kPa/(l/s)] and V3 [0.16±0.08kPa/(l/s)] (p&lt;0.05). Clinical status was also significantly improved compared to baseline; in fact, CAT score changed from an average baseline value of 13-6 and 4 (V2 and V3, respectively) (p&lt;0.05). A correlation was found between CAT percentage change values and the corresponding ones of R5-R20 (r=- 0.329, p=0.045) and RV/TLC (r=0.354, p=0.029).CONCLUSIONS: In COPD patients, treatment with BDP/FF extra-fine formulation improved functional parameters related to small airway disease as well as the disease impact on health status.TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04421742

Impact of SARS-CoV-2 Infection in Children with Asthma and Impact of COVID-19 Vaccination: Current Evidence and Review of the Literature

The clinical aspects of SARS-CoV-2 infection, as well as the COVID-19 vaccines' safety, efficacy and effectiveness in pediatric patients with asthma, are crucial to adapting clinical management in this fragile population and for prevention strategies. The aim of this narrative review was to evaluate the impact of SARS-CoV-2 infection in children with asthma and the impact of COVID-19 vaccination. Systematic research using the principal medical databases was conducted using specific search query strings from the early spreading of COVID-19 globally until March 2023; further relevant data were drawn from the main national and supranational institutions. No significant differences in SARS-CoV-2 incidence and morbidity were found in asthmatic pediatric patients compared to non-asthmatic ones; however, subjects with uncontrolled asthma were found to be at increased risk of developing a serious disease during SARS-CoV-2 infection. Regarding COVID-19 vaccines, accumulating data support their safety, efficacy and effectiveness on asthmatic children regardless of asthma severity. Further cohort-based studies are needed as the evidence of new epidemic waves caused by new viral variants makes the current knowledge outdated