Small Airway Dysfunction Research Articles

Central airway and peripheral lung structures in airway disease-dominant COPD.

The concept that the small airway is a primary pathological site for all COPD phenotypes has been challenged by recent findings that the disease starts from the central airways in COPD subgroups and that a smaller central airway tree increases COPD risk. This study aimed to examine whether the computed tomography (CT)-based airway disease-dominant (AD) subtype, defined using the central airway dimension, was less associated with small airway dysfunction (SAD) on CT, compared to the emphysema-dominant (ED) subtype.COPD patients were categorised into mild, AD, ED and mixed groups based on wall area per cent (WA%) of the segmental airways and low attenuation volume per cent in the Kyoto–Himeji (n=189) and Hokkaido COPD cohorts (n=93). The volume per cent of SAD regions (SAD%) was obtained by nonrigidly registering inspiratory and expiratory CT.The AD group had a lower SAD% than the ED group and similar SAD% to the mild group. The AD group had a smaller lumen size of airways proximal to the segmental airways and more frequent asthma history before age 40 years than the ED group. In multivariable analyses, while the AD and ED groups were similarly associated with greater airflow limitation, the ED, but not the AD, group was associated with greater SAD%, whereas the AD, but not the ED, group was associated with a smaller central airway size.The CT-based AD COPD subtype might be associated with a smaller central airway tree and asthma history, but not with peripheral lung pathologies including small airway disease, unlike the ED subtype.

Prevalence of small airways dysfunction in asthma with- and without-fixed airflow obstruction and chronic obstructive pulmonary disease.

Small airways dysfunction (SAD) is not uncommon in asthma without fixed airflow obstruction (FAO). We aimed to determine if SAD in non-FAO asthma is different from FAO-asthma and COPD. Cases of obstructive airway diseases who underwent spirometry, plethysmography, and impulse oscillometry [resistance at 5 Hz (R5) and at 20 Hz (R20), peripheral resistance (R5-R20), and reactance area (AX)] were reviewed, and classified as; 1) COPD, 2) FAO-asthma, and 3) non-FAO asthma. FAO was defined as post-bronchodilator (post-BD) FEV1/ FVC < 0.7. SAD was considered if 1) RV/TLC ≥ 40%, or 2) post-BD R5-R20 ≥ 0.075 kPa.L-1s. A total of 73 patients (22 COPD, 24 FAO-asthma, and 27 non-FAO asthma) were analyzed. RV/TLC ratio was higher in FAO-asthma and COPD (45 ± 5% and 42 ± 8%) than in non-FAO asthma (32 ± 8%), p < 0.001. Post-BD values of R5-R20 and AX (median; range) were higher in FAO-asthma (0.17; 0.08, 0.47, 13.24; 6.52, 82.11) than in non-FAO asthma (0.11; 0.03, 0.23, 8.63; 2.40, 22.02), p = 0.007 and p = 0.017, respectively. The prevalence of SAD among diagnosis group by RV/TLC criterion was different (95%, 59%, and 15% in FAO-asthma, COPD, and non-FAO asthma, p < 0.001), but those were not observed by R5-R20 criterion (95%, 68%, and 77%, p = 0.052). SAD in non-FAO asthma was less prevalent than FAO-asthma and COPD.

Results and analysis of pulmonary function examination in 76 698 cases of physical examination crowd in Henain Province

Objective: Pulmonary function testing (PFT) and electrocardiograph (ECG) are the vital components of the cardiopulmonary exercise test (CPET). This study is to investigate clinical characteristics of abnormal PFT as pulmonary ventilation dysfunction, small airway dysfunction and gas exchange (diffusion) dysfunction. Methods: Across-sectional study was conducted The 76 698 outpatient subjects who received health examination from December 2016 to February 2019 in Henan Provincial People's Hospital were recruited. The results of the ECG, PFT were compared among different sex and age sub-groups. Then the severity of their impaired PFT were analyzed. Results: Among 76 698 subjects, 39 237 subjects were male and 37 461 subjects were female. There were total 71.04% patients with abnormal ECG. There were total 28 273 (36.86%) patients with abnormal pulmonary ventilation function. The 17 570 patients (44.78%) (17 570/39 237) were male, 10 703 patients (28.57%) (10 703/37 461) were female, both the number and percentage of abnormal pulmonary ventilation function in male was significantly more than these in female (P<0.01). The percentage detectable rates of male were significant higher than that of female in all the different age sub-groups: 20~29, 30~39, 40~49, 50~59, 60~69 and ≥70 year (P<0.01). The total detectable abnormal rate of small airway dysfunction were 43 160 and 56.26% (43 160/76 698). The 57.73% (22 661/39 237) in male was significantly higher than 54.72% (20 499/37 461) in female (x2=74.87, P<0.01). The detectable abnormal rate of small airway dysfunction in male were lower than female in 30~39 year and 40~49year sub-groups (P<0.05), but were significantly higher in 20~29, 50~59, 60~69, and ≥70 yr sub-groups (P<0.05). Abnormal gas exchange (diffusion) dysfunction were detected in 28.54% (12 940/45 107) subjects. They were 7 433 (30.55%) in male,and 5 507 (26.50%)in female with significant gender difference (P<0.05). The abnormal diffusion detectable rate in 30~39 year sub-group was significant higher in female than in male (P<0.05), and were slightly higher without significant difference in 20~29 and 40~49 year sub-groups (P>0.05), but were significant lower in female than male in 50~59, 60~69 and ≥70 year sub-groups (P<0.05). Conclusion: The abnormal detectable rates in ECG, pulmonary ventilation dysfunction, gas exchange dysfunction and small airway dysfunction were higher in male than female, and higher in elder ≥70 year subgroup than all other younger age subgroups.

Small airways in asthma: from bench-to-bedside.

Historically, asthma was considered a disease predominantly of the large airways, but gradually small airways have been recognized as the major site of airflow obstruction. Small airway dysfunction (SAD) significantly contributes to the pathophysiology of asthma, and it is present across all asthma severities. Promising preclinical findings documented enhanced beneficial effects of combination therapies on small airways compared to monocomponents, thus it was questioned whether this could translate into further clinical implications from bench-to-bedside. The aim of this review was to systematically assess the state of the art of small airway involvement in asthma, especially in response to different pharmacological treatments acting on the respiratory system. A comprehensive literature search was performed in MEDLINE for randomized controlled trials (RCTs) characterizing the impact on small airways of different pharmacological treatments acting on the respiratory system. The results were extracted and reported via qualitative synthesis. Overall, 63 studies were identified from the literature search, whereas 23 RCTs met the inclusion criteria. Evidence confirms that both drug particle size and the type of inhalation devices represent two of the most important variables for an effective peripheral lung distribution. Despite the numerous methodological tools to detect SAD, there is still no gold standard diagnostic method to assess small airways, especially in severe asthma. Further research should be directed to improve primary and secondary prevention strategies by supporting the combined approach of different non-invasive techniques for an early detection of peripheral abnormalities and optimization of asthma therapy.

The diagnosis of asthma. Can physiological tests of small airways function help?

Asthma is a common, chronic, and heterogeneous disease with a global impact and substantial economic costs. It is also associated with significant mortality and morbidity and the burden of undiagnosed asthma is significant. Asthma can be difficult to diagnose as there is no gold standard test and, while spirometry is central in diagnosing asthma, it may not be sufficient to confirm or exclude the diagnosis. The most commonly reported spirometric measures (forced expiratory volume in one second (FEV1) and forced vital capacity assess function in the larger airways. However, small airway dysfunction is highly prevalent in asthma and some studies suggest small airway involvement is one of the earliest disease manifestations. Moreover, there are new inhaled therapies with ultrafine particles that are specifically designed to target the small airways. Potentially, tests of small airways may more accurately diagnose early or mild asthma and assess the response to treatment than spirometry. Furthermore, some assessment techniques do not rely on forced ventilatory manoeuvres and may, therefore, be easier for certain groups to perform. This review discusses the current evidence of small airways tests in asthma and future research that may be needed to further assess their utility.

Small airways dysfunction and the state of lung function in mild asthma

Aim . To assess the state of pulmonary function in patients with mild asthma, depending on the state of the small airways. Materials and methods . The study included 114 patients with partially controlled mild asthma (average age 45.12±2.18 years). Depending on the state of the small airways, patients were divided into two groups: first group ‒ 94 patients without small airways dysfunction (SAD) (82%); second group – 20 patients with SAD (18%). The control group consisted of 25 healthy volunteers. Results . It was found that in the group of asthma patients with SAD, in comparison with healthy, a decrease in almost all spirometry indicators was detected, and generalized bronchial obstruction was diagnosed in 55% of cases. Characteristic of asthma patients with SAD was a decrease in the vital capacity of the lungs (VC) by 16% (p&lt;0.001) and the inspiratory capacity (IC) – by 14% (p=0.005) in comparison with patients without SAD. These indicators are used to determine the total lung capacity (TLC=VC+RV and TLC=IC+FRC), where RV is the residual volume, and FRC is the functional residual capacity. It follows that in the case of normal values of TLC, according to spirometry data, with a decrease in VC, it is possible to indirectly judge an increase in RV and the formation of “air traps”, with a decrease in IC – an increase in FRC and the development of hyperinflation of the lungs. Conclusion . The study showed that in patients with mild asthma, SAD was diagnosed in 18% of cases, and it makes a significant contribution to changes in lung function. In mild asthma, SAD is accompanied by generalized bronchial obstruction in 55% of cases. With a decrease in VC and IC according to spirometry data in patients with mild asthma, it is possible to indirectly judge the formation of “air traps”, the development of lung hyperinflation, and consequently, the small airways dysfunction.

Diagnosis of small airway dysfunction in patients with chronic obstructive pulmonary disease

Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Background: Small airway dysfunction (SAD) is a functional hallmark of chronic obstructive pulmonary disease (COPD). However, SAD prevalence and its role in COPD pathophysiology are not yet sufficiently studied.Aim: To assess the prevalence of SAD in COPD patients by various functional diagnostic methods, such as spirometry, body plethysmography, and impulse oscillometry (IOS).Materials and methods: This was an cross-sectional study. Spirometry, body plethysmography and IOS were used in 132 COPD patients in remission under standard anti-COPD treatments. The presence of SAD was confirmed by at least one of the following criteria or their combination: 1) by spirometry: the difference between vital capacity (VC) and forced vital capacity (FVC) &gt; 10%; 2) the presence of air trapping by body plethysmography; 3) identification of the frequency dependence of the resistive resistance at 5 to 20 Hz (R5 - R20 &gt; 0.07 kPa x s/l), as assessed by IOS.Results: Mean forced expiratory volume in 1 s (FEV1) was 42.9% of predicted. Depending on the severity of the obstruction, the patients were divided into 4 groups: 7 patients (group 1) had the obstruction corresponding to GOLD 1 stage, 37 (group 2) to GOLD 2, 49 (group 3) to GOLD 3, and 39 (group 4) to GOLD 4. SAD was found in 96% of COPD patients, whereas in those with severe obstruction (GOLD 3-4), it was present in 100% of the cases. By spirometry, SAD was identified only in 67% of COPD patients, by body plethysmography in 75% of COPD patients (in those with severe obstruction (GOLD 3 and 4) in 88 and 97%, respectively). With IOS, it was possible to identify SAD in 94% of patients and in 100% of those with severe obstruction (GOLD 3-4).Conclusion: With deterioration of obstructive pulmonary ventilation abnormalities in COPD patients, there is a progressive increase in small airway dysfunction. Impulse oscillometry seems to be the most effective method for diagnosis of small airway dysfunction, as it helped to identify SAD in 94% of COPD patients and in 100% of those with severe and very severe obstruction.

Small Airways Dysfunction and Bronchial Hyper-Responsiveness in Cough Variant Asthma.

BackgroundCough variant asthma (CVA) is one kind of atypical asthma. The study was to compare spirometric parameters of small airways and the degree of bronchial hyper-responsiveness (BHR) between CVA and classic asthma (CA), and examine the relationship between BHR and small airways to determine the accuracy of these markers as indicators of CVA.MethodsA total of 825 asthmatic patients were screened for the study, and 614 were included. All patients performed spirometry and underwent a bronchial challenge with methacholine.ResultsThe number of small airways dysfunctions in the CVA group was less than those of the CA group with MMEF% predicted (70% vs 80.91%, P=0.002) and FEF50% predicted (62.71% vs 73.5%, P=0.004). The degree of small airways dysfunction was less in the CVA group compared with the CA group (P<0.001). Significant positive correlations were observed between the FEV1 level below 20% of the baseline value (PD20) and MMEF% predicted (r=0.282, P<0.001), FEF50% predicted (r=0.2522, P<0.001), and FEF75% predicted (r=0.2504, P<0.001) in patients with CVA. The area under curve (AUC) of MMEF, FEF50, and FEF75 (% predicted) was 0.615, 0.621, and 0.606, respectively. In addition, 0.17 mcg of PD20 was the best diagnostic value for CVA, with an AUC of 0.582 (P=0.001).ConclusionSmall airway dysfunction is milder in CVA. The value of BHR combined with small airways in CVA prediction, which was significant, but not enough to be clinically useful.

Small Airway Disease in Pediatric Asthma: the Who, What, When, Where, Why, and How to Remediate. A Review and Commentary.

Asthma affects all portions of the airways. Small airways, however, comprise a substantial component of the conducting lung air flow. In asthma, inflammatory processes can affect the whole respiratory tract, from central to peripheral/small airways. The emphasis in adult and pediatric respiratory disease clinics is to focus on large airway obstruction and reversibility. This information, although valuable, underemphasizes a large portion of the conduction airway of asthmatics. Standard descriptions of asthma management focus on a multiple medication approaches. We particularly focused on the management of asthma in the international guidelines for the Global Initiative for Asthma (GINA). Overall, however, minimal attention is placed on the small airway pool in asthma medical management. We took the opportunity to thoroughly review and present specific data from the adult asthma literature which supported the concept that small airway abnormalities may play a role in the pathogenesis and clinical expression of asthma. Based on the conclusions of the adult asthma literature, we here present a thorough review of the literature as it relates to small airway disease in children with asthma. We used, collectively, individual data sources of data to expand the information available from standard diagnostic techniques, especially spirometry, in the evaluation of small airway disease. As the pharmacological approaches to moderate to severe asthma are advancing rapidly into the realm of biologics, we sought to present potential pharmacological options for small airway dysfunction in pediatrics prior to biological modifier intervention.

Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD

Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline. Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation? Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n= 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n= 22) underwent the forced oscillation technique (resistance at 5Hz minus 19Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions. Sacin was significantly higher in the COPD FE group compared with the IFE group (P= .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P= .001, r= 0.795), AX (P= .049, ρ= 0.560), residual volume to total lung capacity ratio (P= .004, r= 0.730), and the mean lung density of the paired CT scans (P= .018, r= 0.639). Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

Prevalence and features of IOS-defined small airway disease across asthma severities

BackgroundImpulse oscillometry (IOS) is a noninvasive method based on the forced oscillation technique able to detect small airway dysfunction (SAD) in asthma. We aimed to analyze the prevalence and the functional features of IOS-defined SAD across the different Global Initiative for Asthma (GINA) steps. MethodsA cross-sectional, single-center study in which 400 consecutive adult patients with physician-diagnosed, community-managed asthma underwent standard spirometry and IOS, and were stratified by stepwise GINA classification. SAD was defined by IOS as a fall in resistance from 5 to 20 Hz [R5–R20]>0.07kPa × s × L−1. ResultsThe prevalence of IOS-defined SAD ranged between 58.3% (GINA step 2) and 78.6% (GINA step 5), without statistically significant difference within GINA steps (p > 0.05 in all comparisons). Isolated SAD (i.e. without proximal airways involvement) was similarly represented across GINA steps 2–4. Peripheral airways resistance (R5-R20) tended to a progressive increase with the worsening of GINA steps, and was significantly higher in steps 4–5 compared to the other steps (p < 0.05).The proportion of patients with FEF25–75%-defined SAD (<60%) was lower than the IOS-defined one in GINA steps 2–4 (p < 0.05). Only non-significant or weak inverse correlations between R5-R20 and FEF25–75% were observed within each GINA step, with the exception of GINA step 5, which showed a strong, inverse correlation (r = −0.80, p = 0.0005). ConclusionsThis study shows that first, IOS-defined SAD is overwhelmingly present across asthma severities; second, airways resistance increases with the worsening of GINA steps; and third, SAD may be overlooked by standard spirometry, especially in milder asthma.

Forced oscillation measurements in patients after lobectomy - A comparative analysis with IPF and COPD patients.

Forced oscillation technique (FOT) is becoming increasingly widespread measurement method used for assessment of lung function. In the present study, we attempted to assess FOT values in patients after lobectomy in comparison with IPF and COPD patients. Twenty-two patients after lobectomy due to lung cancer stage I or II, 28 patients with idiopathic pulmonary fibrosis and 17 patients with chronic obstructive pulmonary disease were enrolled in the study. All patients performed spirometry (FEV1 , FVC, FEV1 /FVC, MEF50 , MEF25 , FEF25-75 , MIF50 ), plethysmography (Raw , TLC, RV, RV/TLC) and a test using the forced oscillation technique- resistance (R at 5Hz, 11Hz and 19Hz, inspiratory, expiratory and total), reactance (Xat 5Hz, 11Hz, inspiratory, expiratory and total), Fres and expiratory flow limitation (∆X). The ANOVA Kruskal-Wallis test followed by a multiple comparison test were used to evaluate the differences in oscillatory parameters between-groups. Patients after lobectomy presented reduced X5, X11 and moderately increased R5, R11, R19, R5-19, ∆X and Fres. Rinsp 5 weresignificantly higher when compared with IPF patients (P=0.001). In lobectomy patients R5, X5, X11, ∆X and Fres were significantly less affected when compared with patients with COPD (P<0.05 for all values). R5-19, which reflects small airways dysfunction, occurred to be similarly elevated as in COPD patients (0.5 vs 0.6 cmH2 O/L/s).Abnormalities of reactance at 11Hz were observed more frequently than at 5Hz in all groups of patients. Patients after lobectomy due to lung cancer presented FOT abnormalities, which could be caused by lung parenchymal abnormalities following recent thoracic surgery.

Functional parameters of small airways can guide bronchodilator use in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) may present comorbid obstructive lung diseases with small airway dysfunction (SAD). Existing guidelines suggest that inhaled bronchodilators should be used if the ratio of forced expiratory volume in the 1st second and forced vital capacity (FEV1/FVC) < 0.7 in IPF. However, most IPF patients have FEV1/FVC > 0.7 even with coexisting emphysema. We retrospectively enrolled IPF patients who were registered at our outpatient clinic. At baseline, 63 patients completed computed tomography (CT) scans, lung function measurements, and symptom questionnaires. Among these patients, 54 (85.71%) underwent antifibrotic treatment and 38 (60.32%) underwent long-acting bronchodilator treatment. The median FEV1/FVC was 0.86. Not all patients treated with bronchodilators showed significant changes in lung function. IPF patients with SAD, determined by IOS parameters, showed significant improvement in FEV1, FEF25–75%, and symptom scores after bronchodilator treatment. Bronchodilator efficacy was not observed in patients without SAD. CT-confirmed emphysema was seen in 34.92% of patients. There were no changes in lung function or symptom scores after bronchodilator treatment in patients with emphysema. In conclusion, FEV1/FVC cannot reflect the airflow limitation in IPF. Emphysema in IPF is not a deciding factor in whether patients should receive bronchodilator treatment. IOS parameters may be useful to guide bronchodilator therapy in patients with IPF coexisting with SAD.

Impaired small airway function in non-asthmatic chronic rhinosinusitis with nasal polyps.

There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non-asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non-asthmatic patients with CRSwNPs remains unclear. This study analysed the lung function of non-asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs. The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non-asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3years (mean [standard deviation], 42.47±8.38months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients. Non-asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75 ) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non-asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non-asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type-2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non-asthmatic CRSwNP patients was related to serum IgE levels. This study provides evidence that non-asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type-2 inflammation.

SMALL AIRWAYS DISEASE AND Z-ALPHA1-ANTITRYPSIN POLYMERS: IS THERE A CORRELATION?

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: The aim of the study was to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, comparing with matched healthy PiMM subjects. METHODS: We enrolled 17 asymptomatic non-smoker subjects: 9 PiZZ and 8 PiMM as controls, without obstructive ventilatory defect (i.e.: normal FEV1/VC ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in PiZZ patients. ELISA test was applied to search for Z-AAT polymers. RESULTS: The PiZZ subjects showed normal lung volumes and DLCO values. However, In comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.5±0.4 N2/L vs 1.1±0.3 N2/L) and the closing volume/vital capacity ratio (14.3±4.5 % vs 9.5±5.3 %) (p<0.05) in the PiZZ subjects. The ELISA test detected the presence of Z-AAT polymers in 4 PiZZ patients. No correlations were found between polymers levels and any functional respiratory parameter. CONCLUSIONS: PiZZ subjects showed small airways dysfunction when compared to PiMM subjects. Surprisingly, Z-AAT polymers were found only in 4 PiZZ subjects; this is probably due to the sample methodology. New studies are needed to evaluate the correlation between bronchial Z-AAT polymers and small airway impairment in subjects with Z-AAT deficiency. CLINICAL IMPLICATIONS: The presence of Alpha1-Antitrypsin (AAT) polymers that are pro-inflammatory has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (Respir Res, 2014 Sep 14;15:112), suggesting a possible role in the development of COPD. DISCLOSURES: No relevant relationships by Marianna Arici, source=Web Response No relevant relationships by Jordan Franz Giordani, source=Web Response No relevant relationships by Guido Levi, source=Web Response No relevant relationships by Laura Pini, source=Web Response No relevant relationships by Chiara Rocchetti, source=Web Response No relevant relationships by Claudio Tantucci, source=Web Response No relevant relationships by Laura Tiberio, source=Web Response

Airway Deposition of Extrafine Inhaled Triple Therapy in Patients with COPD: A Model Approach Based on Functional Respiratory Imaging Computer Simulations.

IntroductionThere is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs.Materials and MethodsLung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients’ high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition.ResultsHRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were <1, indicating greater peripheral than central deposition (0.48±0.13, 0.48±0.13 and 0.49±0.13 for BDP, FF and GB, respectively; 1.96±0.84, 0.97±0.34 and 1.20±0.48 for FluF, VI and UMEC, respectively).ConclusionsPeripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB.

EFFECT OF SWITCHING FROM MULTI-INHALER NON-EXTRA FINE TO SINGLE-INHALER EXTRA FINE TRIPLE THERAPHY ON REGIONAL BRONCHODILATION AND VENTILATION IN PATIENTS WITH SEVERE COPD

EFFECT OF SWITCHING FROM MULTI-INHALER NON-EXTRA FINE TO SINGLE-INHALER EXTRA FINE TRIPLE THERAPHY ON REGIONAL BRONCHODILATION AND VENTILATION IN PATIENTS WITH SEVERE COPD

Clinical Outcomes of Male Subjects With Moderate COPD Based on Maximum Mid-Expiratory Flow.

Although FEV1 and FEV1/FVC are accepted as standard parameters in treatment follow-up, these parameters have a limited ability to predict clinical outcomes in patients with COPD. However, small airways dysfunction, which is determined by maximum mid-expiratory flow, is variable in the same stage of patients with COPD, even if their FEV1 and FEV1/FVC are similar. The aim of this study was to compare pulmonary function, the severity of perceived dyspnea, the severity of fatigue, physical activity level, and health-related quality of life based on the severity of small airways dysfunction in male subjects with moderate COPD. The study consisted of 96 subjects with moderate COPD. Pulmonary function tests, the distance achieved on the 6-min walk test, the modified Medical Research Council Dyspnea Scale, the International Physical Activity Questionnaire - short form, the Fatigue Severity Scale, the St George Respiratory Questionnaire, and Short Form 36 questionnaire were evaluated in all subjects. After calculating the mean percent of predicted maximum mid-expiratory flow for the entire sample, subjects were divided into 2 groups: below average (Group 1, n = 54 subjects) and above average (Group 2, n = 42 subjects). There were no differences between the groups in age, body mass index, cigarette consumption, percent of predicted FEV1, and FEV1/FVC (P = .55, .61, .19, .09, and .15, respectively). Scores from the Fatigue Severity Scale and the modified Medical Research Council dyspnea scale were significantly higher in Group 1 (P = .003 and P = .002, respectively); in addition, results from the 6-min walk test and the International Physical Activity Questionnaire - short form scores were significantly lower (P = .001 and P < .001, respectively). Increased small airways dysfunction led to increased perception of dyspnea and fatigue, as well as poor exercise capacity and health-related quality of life in male subjects with COPD. We suggest that it may be useful to consider the maximum mid-expiratory flow in addition to FEV1 and FEV1/FVC in the treatment and follow-up of male patients with moderate COPD.

Dyspnea and Exercise Limitation in Mild COPD: The Value of CPET

The majority of smokers with chronic obstructive pulmonary disease (COPD) have mild airflow limitation as determined by simple spirometry. Although small airway dysfunction is the hallmark of COPD, many studies attest to complex heterogeneous physiological impairments beyond increased airway resistance. These impairments are related to inflammation of lung parenchyma and its microvasculature, which is obscured by simple spirometry. Recent studies using advanced radiological imaging have highlighted significant structural abnormalities in smokers with relatively preserved spirometry. These important studies have generated considerable interest and have reinforced the pressing need to better understand the physiological consequences of various morphological abnormalities, and their impact on the clinical outcomes and natural history of COPD. The overarching objective of this review is to provide a concise overview of the importance and utility of cardiopulmonary exercise testing (CPET) in clinical and research settings. CPET uniquely allows evaluation of integrated abnormalities of the respiratory, cardio-circulatory, metabolic, peripheral muscle and neurosensory systems during increases in physiologic stress. This brief review examines the results of recent studies in mild COPD that have uncovered consistent derangements in pulmonary gas exchange and development of “restrictive” dynamic mechanics that together contribute to exercise intolerance. We examine the evidence that compensatory increases in inspiratory neural drive from respiratory control centers are required during exercise in mild COPD to maintain ventilation commensurate with increasing metabolic demand. The ultimate clinical consequences of this high inspiratory neural drive are earlier onset of critical respiratory mechanical constraints and increased perceived respiratory discomfort at relatively low exercise intensities.

Extrafine combination beclomethasone dipropionate/ formoterol therapy in obstructive lung diseases

Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airways. Inhaled bronchodilators and corticosteroids are the cornerstone of pharmacological long-term treatment for asthma and COPD. The efficacy of any topical inhaled medication is dependent upon successful distribution of the drug to the site of disease. Targeting small airways inflammation in severe asthma and COPD are critically important as the combined surface area of small airways far exceeds the surface area that large central airways provide. Small airway dysfunction in BA is associated with increased asthma symptoms, worse asthma control and an increased number of exacerbations. Chronic inflammation in COPD causes structural alterations and narrowing of particularly the small airways. The extrafine combination of beclomethasone dipropionate/formoterol (BDP/F) enables drug delivery to both the large and small airways, and allows the clinical benefits to be achieved with a lower corticosteroid dose. The use of extrafine BDP/F is more effective in achievement asthma control and reduce COPD exacerbations. If it is necessary to continue ICS as part of a double or triple COPD therapy extrafine fixed combination of BDP/F can be considered as the drug of choice and optimal replacement of the ICS molecule.