Baseline FEV1 Research Articles

Routine spirometry in cystic fibrosis patients: impact on pulmonary exacerbation diagnosis and FEV1 decline.

ABSTRACTObjective:Pulmonary disease in cystic fibrosis (CF) is characterised by recurrent episodes of pulmonary exacerbations (PExs), with acute and long-term declines in lung function (FEV1). The study sought to determine whether routine spirometry increases the frequency of PEx diagnosis, resulting in benefits to long-term pulmonary function. Methods:CF patients in the 5- to 18-year age bracket were followed for 1 year, during which they underwent spirometry before every medical visit. The main variables were the frequency of PEx diagnosis and use of antibiotics; the use of spirometry as a criterion for PEx diagnosis (a decline ≥ 10% in baseline FEV1); and median percent predicted FEV1 over time. The data were compared with those for the previous 24-month period, when spirometry was performed electively every 6 months. Results:The study included 80 CF patients. PExs were diagnosed in 27.5% of the visits, with a mean frequency of 1.44 PExs per patient/year in 2014 vs. 0.88 PExs per patient/year in 2012 (p = 0.0001) and 1.15 PExs per patient/year in 2013 (p = 0.05). FEV1 was used as a diagnostic feature in 83.5% of PExs. In 21.9% of PExs, the decision to initiate antibiotics was solely based on an acute decline in FEV1. The median percent predicted FEV1 during the follow-up year was 85.7%, being 78.5% in 2013 and 76.8% in 2012 (p > 0.05). The median percent predicted FEV1 remained above 80% during the two years after the study. Conclusions:Routine spirometry is associated with higher rates of diagnosis and treatment of PExs, possibly impacting long-term pulmonary function.

Short-acting inhaled bronchodilators for cystic fibrosis.

Short-acting inhaled bronchodilators for cystic fibrosis.

Chronic Bronchial Infection Is Associated with More Rapid Lung Function Decline in Chronic Obstructive Pulmonary Disease.

Rationale: Some patients with chronic obstructive pulmonary disease (COPD) suffer accelerated lung function (forced expiratory volume in 1 second [FEV1]) decline over time. Objectives: To investigate the relationship between chronic bronchial infection (CBI) and, in particular, the isolation of Pseudomonas aeruginosa (PA), and FEV1 decline in COPD. Methods: Post-hoc analysis of a prospective cohort of 201 patients with COPD followed up every 3-6 months for 84 months. CBI was defined as ⩾3 sputum positive cultures of the same pathogenic micro-organism (PPM) over 1 year. Patients were stratified according to the presence of CBI by any PPM, as well by a single or multiple isolation of PA during follow-up. An adjusted mixed-effects linear regression model was used to investigate the independent effects of CBI and PA isolation on FEV1 decline over time. Results: During follow-up, PPMs were never isolated in 43.3% of patients, in 23.9% of them PPMs were isolated once, and CBI by any PPM was confirmed in 32.8% of participants. FEV1 decline in the entire cohort was 33.7 (95% confidence interval [CI], 21.4-46.1) ml/year. This was significantly increased in patients with CBI by any PPM (57.1 [95% CI, 28.5-79.3] ml/year) and in those in whom PA was isolated at least once (48.5 [95% CI, 27.3-88.2] ml/year). Multivariable analysis showed that the presence of both CBI by any PPM, and at least one PA isolation, were independent factors associated with faster FEV1 decline adjusted by baseline FEV1, presence of bronchiectasis, body mass index, age, exacerbations, smoking status, symptoms, baseline treatment, and comorbidities. Conclusions: The presence of CBI by any PPM, and one or more PA isolation, were independently associated with FEV1 decline in patients with COPD.

185-LB: Pulmonary Function and Diabetes Risk in a Cohort of Black and White Current and Former Smokers

The recent COVID-19 pandemic, which saw an increased risk of subsequent diabetes among persons with COVID-19 as well as greater casualties among persons with diabetes, has brought renewed attention to the role of lung function in diabetes. We tested the relationship of lung function and chronic obstructive pulmonary disease (COPD) with diabetes in a population of current and former smokers. Using data from the COPD Genetic Epidemiology (COPDGene) cohort, we conducted a diabetes follow-up (2012-2018) of a cohort of Black and White current and former smokers with (n=2442) and w/out (n=2214) COPD, aged 39-85 years and w/out diabetes at cohort entry. Lung function was modeled using Forced Expiratory Volume at 1 second % predicted (FEV1%P) . COPD was defined as the ratio of FEV1% to FVC% <0.7. Logistic regression was used to compute ORs (95% CIs) for risk of incident diabetes. The incidence of diabetes was 8% over the five years of follow-up, representing a 43% increase in prevalence. After controlling for age, sex, and race, COPD at baseline was a significant risk factor for diabetes (OR=1.51, 1.21-1.88) . Significant interaction existed between baseline COPD and baseline Fev1%p (p-interaction=0.01) , such that Fev1%p only predicted diabetes among those w/out (OR=0.98, 0.96-0.99) but not among those with COPD at baseline (OR=0.99, 0.99-1.00) . Upon stratification by race, Fev1%p was a significant predictor among Blacks but not Whites, but effect modification by race was not observed. Blacks were at twice the risk of diabetes overall (OR=2.04, 1.59-2.60) and were at 3 times the risk among those w/out COPD (OR=2.91, 1.98-4.27) . BMI increased risk in both races regardless of COPD status; however, a higher BMI was a stronger risk factor for diabetes among Whites than Blacks, particularly for those with baseline COPD (race*BMI interaction p=0.06) . In this large population of current and former smokers, our data suggest that lower lung function prior to the development of COPD is a risk factor for diabetes, particularly among Blacks. BMI is an important risk factor in both races, but appears to play a stronger role among Whites. Disclosure R. B. Conway: None. K. Young: None. Y. Li: Employee; Vertex Pharmaceuticals Incorporated. E. Austin: None. G. L. Kinney: None. Funding National Institutes of Health (U01HL089897)

Daily Inhaled Corticosteroids Treatment Abolishes Airway Hyperresponsiveness to Mannitol in Defence and Police Recruits.

BackgroundAirway hyperresponsiveness (AHR) is a key pathophysiological feature of asthma and causes exercise-induced bronchoconstriction (EIB). Indirect bronchial provocation tests (BPTs) (e.g., exercise, mannitol) aid to diagnose asthma and identify EIB. Daily inhaled corticosteroids (ICS) can abolish AHR caused by indirect stimuli. Where strenuous physical exertion is integral to an occupation, identification of those at risk of EIB is important and documentation of inhibition of AHR with ICS is required before recruitment.Methods/ObjectivesA retrospective analysis was performed on 155 potential recruits with AHR to mannitol who underwent follow-up assessment after daily ICS treatment to determine the proportion that can abolish AHR using ICS and to determine any predictors of the persistence of AHR.ResultsAirway hyperresponsiveness was abolished in the majority (84%, n = 130) over the treatment period (mean ± SD 143 ± 72days), and it was defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (cumulative inhaled dose of mannitol to cause 15% fall in FEV1, PD15) improved from (GeoMean) 183 to 521 mg. Compared with recruits in whom AHR was abolished with daily ICS (i.e., no 15% fall in FEV1 to the maximum cumulative dose of mannitol of 635 mg), in those where AHR remained (16%, n = 25), baseline AHR was more severe (PD15: 85 mg vs. 213 mg, P < 0.001), baseline FEV1% was lower (89 vs. 96%; 95%CI:2–12, P=0.004), and they had a longer follow-up duration (180 vs. 136 days; 13–74, P = 0.006). Baseline FEV1% (adjusted odds ratio 0.85; 95%CI:0.77–0.93), FEV1/FVC (0.78; 0.67–0.90), FEF25−75% (1.15; 1.06–1.25), and airway reactivity to mannitol (%Fall/cumulative dose of mannitol multiplied by 100) (1.07; 1.03–1.11) predicted AHR remaining after daily ICS.ConclusionAirway hyperresponsiveness to mannitol can be abolished after 20 weeks of daily treatment with ICS. Inhibition of AHR is likely due to attenuation of airway inflammation in response to ICS treatment. Increased airway reactivity and lower spirometry variables predicted the persistence of AHR. Thus, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.

The effect of antibiotic changes during treatment of cystic fibrosis pulmonary exacerbations

BackgroundAntibiotics are often changed during treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) who have a poor clinical response. We aimed to characterize the reasons CF providers change antibiotics and examined the effects of antibiotic changes on lung function recovery. MethodsThis was a retrospective cohort study using the Toronto CF Database from 2009 to 2015 of adults and children with CF PEx treated with intravenous antibiotics. The co-primary outcome measure was absolute and relative change in forced expiratory lung volume in 1 s (FEV1) at end of treatment and follow-up. Secondary outcome assessed the proportion of patients returning to > 90% or > 100% previous baseline FEV1. ResultsA total of 399 PEx were included of which 105 had antibiotic changes. Reasons for antibiotic changes included change in antibiotic route prior to discharge (26%), drug reactions (20%), poor FEV1 response (25%), targeting additional microbes (16%) and lack of symptom improvement (13%). In our multivariable analysis, among non-responders (< 90% FEV1 recovery to baseline or lack of symptom improvement at the interim time point), a change in antibiotics was not associated with any significant difference in absolute or relative FEV1 at end of treatment or at follow-up. Antibiotic change in non-responders was not associated with improved return to 90% or 100% baseline FEV1 at end of treatment or follow-up. ConclusionsChanging antibiotics during CF PEx treatment in those with poor clinical response was not associated with any improved FEV1 response or return to baseline lung function.

Annual FEV1 Loss in Patients with Noncystic Fibrosis Bronchiectasis and Affecting Factors.

Bronchiectasis is a chronic respiratory disease characterized by sputum production, cough, and several bronchial infections. Lung function is an important parameter to evaluate and study in patients with bronchiectasis. This study aimed to evaluate the annual changes in forced expiratory volume in one second (FEV1) and related factors in patients with with noncystic fibrosis bronchiectasis. A total of 529 patients who were diagnosed as having bronchiectasis using computed tomography and followed at the bronchiectasis unit of the Cerrahpasa Medical Faculty at Istanbul University between 1996 and 2018 were included in this retrospective study. A total of 153 patients were included in the study. The mean age of the patients was 58.6 ± 16.8 years and 61% (n = 93) were female. The annual change of FEV1 and forced vital capacity was -39 ± 82 (minimum: -585, maximum: 355, median: -26) mL and - 44 ± 91 (minimum: -517, maximum: 303, median: -31) mL, respectively. There was no correlation in FEV1 decline between those with and without Pseudomonas colonization (P = 0.65). No correlation was found between the etiologic factors and the decline of FEV1. A correlation existed only between the first FEV1 and the decline of FEV1 (for the first FEV1%, P = 0.038 [R = -0.17]; for the first FEV1 [mL] P = 0.026 [R = -0.18]). An annual mean FEV1 loss of 39 mL was found in adult patients with noncystic fibrosis bronchiectasis. The annual mean FEV1 decline was found to be associated with the baseline FEV1 value. Physicians should exercise caution in this regard in patients with bronchiectasis with low FEV1 values.

Correlation of Activation Site and Number with the Clinical Response to Bronchial Thermoplasty.

ObjectiveTo investigate the relation of activation site and number with clinical response to bronchial thermoplasty (BT) in refractory asthma patients.MethodsThis work included 106 consecutive refractory asthma patients completing three BT sessions in our hospital from May 2016 to May 2019. Procedure details included recording delivery sites and those in BT. Asthma Control Questionnaire (ACQ) scores and spirometric measurements were recorded 1-day before treatment and 6 months post-treatment to explore the effects of BT activation number and site on clinical response.ResultsACQ score (3.19±1.14 vs 1.26±0.63), forced expiratory volume in 1 sec (FEV1)% predicted (55.53±21.66 vs 66.19±22.50), FEV1 (1.53±0.74 vs 1.93±0.82), and forced vital capacity (FVC) (2.49±0.86 vs 2.92±0.94) significantly increased after three BT sessions compared with pre-session. Major bronchial ablation did not significantly improve BT response in asthma patients. Multivariate logistic regression identified baseline ACQ score and baseline FEV1% predicted as independent factors affecting the clinical response to BT. Correlation and regression analysis revealed a significant linear relationship between baseline ACQ and ACQ improvement, as well as a linear relationship between the third session activation number and ACQ improvement. Based on subgroup analysis of activation number, cohort C (activations ≥ 200) had better lung function, lower non-responding rate, and better long-term effectiveness than the other two cohorts. The activation number in the third BT session showed the strongest predictive ability compared with the first two sessions.ConclusionMain bronchial ablation did not markedly affect clinical response to BT. Baseline ACQ and baseline FEV1% predicted were independent factors affecting clinical response to BT. Increasing the activation number might promote the therapeutic efficacy of BT, and the activation number in the third BT session correlated with and predicted the BT response.

Donor Age and Recipient-Donor Sex and Height Mismatch Are Associated with Abnormal Pulmonary Reactance (X5) in Stable Recipients After Bilateral Lung Transplantation

<h3>Purpose</h3> Respiratory system reactance at 5Hz (X₅) reflects tissue elastance and inertance and is measured using oscillometry, a novel measurement of respiratory mechanics. Abnormal reactance (stiffness) has been observed in baseline and chronic lung allograft dysfunction. This study aims to assess predictors of pulmonary reactance in stable lung transplant (LTx) recipients. <h3>Methods</h3> A cross-sectional study was performed on bilateral lung transplant (LTx) recipients at 2 Australian centres between Jan-20 and Jun-21. Spirometry and oscillometry (TremoFlo C-100) were performed to obtain FEV₁ and FVC and X₅, respectively. Patients with acute and chronic lung allograft dysfunction (LAD) were excluded. Baseline lung allograft dysfunction (BLAD) was defined as failure to achieve FEV₁ or FVC >80%-predicted. Oostveen equations were used to generate predicted X₅ values. Abnormal X₅ was defined as Z-score ≤ -1.64. Logistic regression measured associations between baseline transplant predictors and risk of abnormal X_5. <h3>Results</h3> A total of 326 bilateral lung transplant recipients underwent oscillometry. 173 patients with LAD were excluded and 153 included for final analysis. Patients were at median (IQR) 1.9 (2.7) years after transplant. The median (IQR) concurrent FEV₁ as %-baseline FEV₁ was 96% (7). Abnormal X₅ was detected in 21 (13.7%) and normal X₅ in 132 (86.3%). Increasing donor age (OR 1.03, 95%CI 1.00-1.06, p=0.047), recipient-donor sex mismatch (Male:Female OR 5.15, 95%CI 1.70-15.59, p=0.004), donor-recipient height difference (OR 0.95, 95% CI 0.90-0.99, p=0.027) and spirometric BLAD (OR 7.21, 95%CI 2.59-20.06, p<0.001) were associated with an increased risk of abnormal X_5. <h3>Conclusion</h3> Undersizing of lungs, recipient-donor sex mismatch and increasing donor age are significantly associated with abnormal X₅. Differences in lung volume due to sex and size matching may partly explain this association. Increasing age is associated with decreased lung elastic recoil. Preliminary analysis is limited by the use of recipient anthropometrics to generate predicted values. Longitudinal studies are required to determine if the reactance trajectory may help predict patients at risk of poor outcomes.

Carfilzomib versus Rituximab for Treatment of De Novo Donor Specific Antibodies in Lung Transplant Recipients

<h3>Purpose</h3> De novo donor-specific antibodies (DSA) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSA; however, a comparison of these two agents in LTRs has not been performed. We compared the degree and duration of DSA depletion with CFZ- and RTX-based treatment strategies. <h3>Methods</h3> LTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was change in MFI (ΔMFI) at corresponding loci before and within 6 months of treatment. Secondary outcomes were time to DSA rebound, change in % predicted FEV1 (ΔFEV1) 6 months after treatment, and CLAD-free survival. <h3>Results</h3> We identified 44 LTRs treated with either CFZ or RTX. As 7 LTRs had ≥2 drug events, 53 drug events were identified and divided into 2 groups, CFZ (32%, n=17) and RTX (68%, n=36). The median time from transplant to detection of DSA was 3 months (1, 24). Use of plasmapheresis (PLEX) and IVIG and increases in mycophenolate mofetil (MMF) dose were equivalent in both groups (PLEX, 97% vs 94%, p=0.580; IVIG, 94.4% vs 94.1%, p=0.962; MMF dose increase 61.1% vs 76.5%, p=0.270). Both drugs significantly lowered the MFI at the DQ locus (Figure 1A, 1B), and the median ΔMFI was comparable. The median interval to DSA rebound was shorter in the CFZ group (4.8 vs 15.6 months, p=0.002). Baseline FEV1 and ΔFEV1 after drug administration were lower in the CFZ group than the RTX group (p<0.001 and p=0.002, respectively). CLAD-free survival with a single RTX event was superior to ≥2 drug events (p=0.001) but was comparable with a single CFZ event (p=0.399; Figure 1C). <h3>Conclusion</h3> While both CFZ and RTX reduced the MFI of circulating DSA, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV1 with RTX, CLAD-free survival was comparable in the 2 groups suggesting that both drugs offer a reasonable treatment strategy for DSA in LTRs.

Chronic Lung Allograft Dysfunction: More Than Meets the Eye?

<h3>Purpose</h3> Currently, chronic lung allograft dysfunction (CLAD) is defined as the presence of an irreversible or partly reversible (to ≤ 80% of baseline) decline in FEV1 compared with baseline FEV1 values, persistent for at least 3 months. In established CLAD, total lung capacity (TLC) and chest computed tomography (CT) are required to determine the CLAD phenotype, as this has therapeutic and prognostic significance. Current CLAD phenotypes comprise bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS), Mixed, or Undefined (in patients who do not fit in either of the other phenotypes). However, some patients may present with persistent (> 3 months) chest CT abnormalities suggestive for chronic lung allograft injury/remodelling, without clear spirometric evidence of physiologic lung allograft impairment. <h3>Methods</h3> We report a series of 7 lung transplant recipients demonstrating chronic radiological abnormalities comparable to that seen in CLAD (RAS/mixed), after exclusion of other underlying causes for the observed radiological abnormalities, yet without (significant) pulmonary function decline. <h3>Results</h3> All patients had clear, persistent (> 3 months) radiological signs of chronic lung allograft injury/remodelling, however, not qualifying for formal CLAD diagnosis (i.e. FEV1 decline ≥ 20% from baseline), but instead looming in the potential CLAD area (FEV1 decline ≥ 10% from baseline) or even presenting with normal spirometry on regular pulmonary function testing. <h3>Conclusion</h3> A subgroup of lung transplant recipients may atypically present with chronic parenchymal/interstitial (‘RAS-like') abnormalities on chest CT, without qualifying for the phenotypic definition of CLAD, according to current consensus. This warrants further reflection on the role of spirometry for detection of interstitial lung disease after lung transplantation, the potential need for regular chest CT during post-transplant follow-up, and accuracy of the current CLAD definition regarding physical lung allograft characteristics.

Effect of Inspiratory Muscles Training With Threshold Loading Device in Patients With Chronic Obstructive Pulmonary Disease

Research Objectives To find out the changes of inspiratory muscle strength by manometer, to assess the changes of exercise tolerance by 6MWT, to assess the changes of FEV1 and FVC with the spirometer and to assess the quality of life by COPD assessment test at 0, 2nd, 4th and 6th week in patients with COPD treated with the inspiratory muscles training using threshold loading device. Design Hospital-based quasi-experimental study. Setting The study was conducted at hospitalized care. Participants Participants (N=30) were diagnosed with COPD by attending physicians, age between 40 and 80, and both male and female by convenience sampling method. Interventions The participants received inspiratory muscles training (IMT) with a threshold loading device. Main Outcome Measures The main outcome measures were (1) maximum inspiratory pressure, (2) Forced vital capacity (FVC) and Forced expiratory volume in one second (FEV1), (3) the 6-minute walk test (6-MWT), and (4) the COPD Assessment Test (CAT) questionnaire. Results The baseline maximal inspiratory pressure was 69.9 cmH2O and 16.7±5.8 cmH2O (Mean+SD) at the sixth week, and the p-value was 0.01. At the baseline assessment, FEV1 and FVC were 1.3 L and 1.8 L and 0.68±0.18 (Mean+SD) and 0.46±0.26 (Mean+SD) at the sixth week, and p-value were 0.01 and 0.007. The 6-MWT was 249 meters and 25.8±8.4 (Mean+SD) at the sixth week, and the p-value was 0.008. The CAT score was 11 before intervention and -3.9±2.2 (Mean+SD) at the sixth week, and the p-value was 0.01. Conclusions There were improvements in inspiratory pressure, lung functions, exercise tolerance, and quality of life both clinically and statistically by the IMT with the threshold loading device in this study. Therefore, inspiratory muscles training with a threshold loading device should be used as the routine treatment in patients with COPD. Author(s) Disclosures There is no conflicts and disclosures. To find out the changes of inspiratory muscle strength by manometer, to assess the changes of exercise tolerance by 6MWT, to assess the changes of FEV1 and FVC with the spirometer and to assess the quality of life by COPD assessment test at 0, 2nd, 4th and 6th week in patients with COPD treated with the inspiratory muscles training using threshold loading device. Hospital-based quasi-experimental study. The study was conducted at hospitalized care. Participants (N=30) were diagnosed with COPD by attending physicians, age between 40 and 80, and both male and female by convenience sampling method. The participants received inspiratory muscles training (IMT) with a threshold loading device. The main outcome measures were (1) maximum inspiratory pressure, (2) Forced vital capacity (FVC) and Forced expiratory volume in one second (FEV1), (3) the 6-minute walk test (6-MWT), and (4) the COPD Assessment Test (CAT) questionnaire. The baseline maximal inspiratory pressure was 69.9 cmH2O and 16.7±5.8 cmH2O (Mean+SD) at the sixth week, and the p-value was 0.01. At the baseline assessment, FEV1 and FVC were 1.3 L and 1.8 L and 0.68±0.18 (Mean+SD) and 0.46±0.26 (Mean+SD) at the sixth week, and p-value were 0.01 and 0.007. The 6-MWT was 249 meters and 25.8±8.4 (Mean+SD) at the sixth week, and the p-value was 0.008. The CAT score was 11 before intervention and -3.9±2.2 (Mean+SD) at the sixth week, and the p-value was 0.01. There were improvements in inspiratory pressure, lung functions, exercise tolerance, and quality of life both clinically and statistically by the IMT with the threshold loading device in this study. Therefore, inspiratory muscles training with a threshold loading device should be used as the routine treatment in patients with COPD.

Ventilation Rates Achieved in Eucapnic Voluntary Hyperpnea Challenge and Exercise-Induced Bronchoconstriction Diagnosis in Young Patients with Asthma.

Exercise-induced bronchoconstriction (EIB) affects approximately 50% of young asthma patients, impairing their participation in sports and physical activities. Eucapnic voluntary hyperpnea (EVH) is an approved surrogate challenge to exercise for objective EIB diagnosis, but the required minimum target hyperventilation rates remain unexplored in this population. This study aimed to evaluate the association between the achieved ventilation rates (VRs) during a challenge and EIB-compatible response (EIB-cr) in young asthma patients. This cross-sectional study included 72 asthma patients aged 10-20years. Forced expiratory volume in the first second (FEV1) was measured before and 5, 15, and 30min after the EVH. The target VR was set at 21 times the individual's baseline FEV1. A decrease of > 10% in FEV1 after the challenge was considered an EIB-cr. The challenge was repeated after 48-72h in those without an EIB-cr. Thirty-six individuals had an EIB-cr at initial evaluation. The median VRs achieved was not different between individuals with and without an EIB-cr (19.8 versus 17.9; p = 0.619). The proportion of individuals with an EIB-cr was nor different comparing those who achieved (12/25) or not (24/47) the calculated target VRs (p = 0.804). At the repeated EVH challenge an EIB-cr was observed in 14/36 individuals with a negative response in the first evaluation, with no differences in achieved VRs between the two tests (p = 0.463). Irrespective of the achieved VR, an EIB-compatible response after an EVH challenge must be considered relevant for clinical and therapeutic judgment and negative tests should be repeated.

LIGHT - LTßR Signaling is Essential for Airway Smooth Muscle Remodeling and Asthmatic Airway Hyperresponsiveness

Airway hyperresponsiveness (AHR) and dysregulation of airway smooth muscle cells (ASM) is central to the severity of asthma. However which molecules control ASM in asthmatics is still largely unclear. High levels of the cytokine TNFSF14/LIGHT have been linked to asthma severity and lower baseline FEV1 %predicted, implying signals through either of its receptors, LTbR and HVEM, could directly control ASM dysfunction. We aimed to determine whether signaling via LTbR or HVEM from LIGHT controls ASM hyperreactivity.

Baseline Spirometry as a Predictor of Positive Methacholine Challenge Testing for Exertional Dyspnea.

There are several tests recommended by the American Thoracic Society (ATS) to evaluate for airway hyper-responsiveness (AHR), one of which is methacholine challenge testing (MCT). Few studies have examined the correlation of baseline spirometry to predict AHR in MCT, especially in the younger, relatively healthy military population under clinical evaluation for symptoms of exertional dyspnea. The study aim was to retrospectively correlate baseline spirometry values with MCT responsiveness. This study is a retrospective review of all MCT performed at Brooke Army Medical Center/Wilford Hall Medical Center over a 12-y period; all completed studies were obtained from electronic databases. The following parameters were analyzed from the studies: baseline FEV1, FVC, FEV1/FVC, mid-expiratory flow (FEV25-75%), FEV25-75%/FVC. Studies were categorized based on baseline obstruction, restriction, FEF25-75% lower limit of normal, and response to bronchodilator testing (if completed); these values were compared based on methacholine reactivity and severity. Methacholine challenge studies (n = 1,933) were reviewed and categorized into reactive (n = 577) and nonreactive (n = 1,356) as determined by ATS guidelines. The mean baseline FEV1 (% predicted) with MCT reactivity was 88.0 ± 13.0% versus no MCT reactivity was 92.7 ± 13.0% (P < .001). The mean baseline FVC (% predicted) was 93.1 ± 13.7% versus 95.3 ± 13.5% (P < .001). The mean baseline FEV25-75% (% predicted) was 80.0 ± 22.1% versus 89.0 ± 23.4% (P < .001). Based on partition analysis, methacholine reactivity was most prevalent with baseline obstruction, n = 115 (43%), and in the absence of obstruction, when the FEF25-75% (% predicted) was below 0.70, n = 111 (40%). The negative predictive value with normal spirometry was 73%. The analysis of baseline spirometry prior to MCT proved useful in the evaluation of exertional dyspnea in a military population. The presence of airways obstruction (FEV1/FVC < lower limit of the normal range) followed by a reduction in FEV25-75% < 70% predicted showed a positive correlation with underlying AHR. In patients with exertional dyspnea and normal baseline spirometry, the use of the FEF25-75% may be a useful surrogate measurement to predict reactivity during MCT and consideration for additional testing or treatment.

Intermittent prophylactic antibiotics for bronchiectasis.

Intermittent prophylactic antibiotics for bronchiectasis.

Effect of inhaled budesonide/formoterol fumarate dihydrate delivered via two different devices on lung function in patients with COPD and low peak inspiratory flow.

Background and aims:Low peak inspiratory flow (PIF) is common following severe exacerbations of chronic obstructive pulmonary disease (COPD). Patients with COPD and low PIF may be at risk of suboptimal delivery of inhaled therapies to the airways, especially when using devices such as dry powder inhalers (DPIs), which require greater inspiratory effort than metered dose inhalers (MDIs). We report the results from a 2-week crossover study evaluating the effects of inhaled dual therapy with budesonide/formoterol fumarate dihydrate with an MDI with a spacer versus a DPI in patients with COPD and low PIF.Methods:This randomized, open-label, two-period (each 1 week in duration) crossover efficacy and safety study included patients with severe-to-very severe COPD and PIF < 50 L/min (NCT04078126). Patients were randomized 1:1 to twice-daily budesonide/formoterol fumarate dihydrate MDI (BFF MDI) 320/10 µg with a spacer for 1 week followed by twice-daily budesonide/formoterol fumarate dihydrate DPI (BUD/FORM DPI) 320/9 µg for 1 week, or the inverse. The primary endpoint was peak change from baseline in forced expiratory volume in 1 s (FEV1) within 4 h post-dose following 1 week of treatment. Other assessments included pre-dose lung function, pharmacokinetics, and safety, as assessed by adverse events.Results:The modified intention-to-treat analysis set comprised 30 patients (mean age: 66.9 years; mean baseline FEV1: 766 mL; mean COPD assessment test score: 22.20). Following 1 week of treatment, both BFF MDI and BUD/FORM DPI improved mean [95% confidence interval (CI)] peak FEV1 4 h post-dose [256 (190, 322) mL and 274 (208, 340) mL, respectively]. No clinically meaningful difference between treatments was observed for any lung function endpoint. There were no unexpected safety findings.Conclusion:Dual therapy with BFF MDI and with BUD/FORM DPI led to improvements in lung function in patients with severe-to-very severe COPD and low PIF.

A prospective observational evaluation of treatment outcomes of patients with chronic obstructive pulmonary disease and peripheral blood eosinophilia.

This study aimed to compare two groups of patients with Chronic Obstructive Lung Disease (COPD) and blood eosinophil values of ≥300 cells/ µL. The patients were followed up for one year in two groups, one receiving inhaled corticosteroids (ICS) and the other not receiving ICS in terms of exacerbation rates, the incidence of pneumonia, mortality rates, FEV1, FVC and FEF25-75 changes, the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores. Stable patients, who presented to the University Medical Faculty Chest diseases outpatient clinic and diagnosed with COPD according to pulmonary function test results and GOLD stages 2-4 according to the 2017 GOLD criteria and with blood eosinophil counts of ≥ 300 cells/ µL were included in the study. 85 patients were included in the study, of which 76.5% (n= 65) were males. There were no significant differences between the 38 patients receiving ICS and the 47 patients not receiving ICS regarding baseline FEV1, FVC, FEF25- 75 absolute values and percentages, and FEV1, FVC values controlled at month six and month 12, and FEF25-75 absolute values and percentages at month six (p> 0.05). However, the difference between the baseline and month 12 absolute values and percentages of FEF25-75 was statistically significant, and the decrease from baseline was greater in the group receiving ICS (p< 0.05). The difference in CAT and mMRC scores were statistically significant at month six and month nine in favor of the group receiving ICS (p< 0.05). The median number of moderate and severe exacerbations were both one (min: 0, max:3) in the group receiving ICS (n= 38) and in the one not receiving ICS (n= 47). The difference of exacerbation rates in both groups were not statistically significant (p> 0.05). In this study, it was determined that exacerbation rates of eosinophilic COPD patients did not differ depending on the use of ICS in a one-year period. Nevertheless, the 12-month FEF25-75 values of patients not using ICS were lower to a lesser extent, while the CAT and mMRC scores improved in favor of ICS users at different months in the one-year follow-up.

Ceftaroline versus vancomycin for treatment of acute pulmonary exacerbations of cystic fibrosis in adults

Vancomycin remains a first-line treatment for methicillin-resistant Staphylococcus aureus (MRSA)-mediated acute pulmonary exacerbations (APEs) in adult cystic fibrosis (CF) patients; however, optimal alternatives remain poorly defined. The aim of this study was to determine the safety and efficacy of ceftaroline for MRSA-mediated APEs of CF in adults. We conducted a retrospective, observational cohort study comparing ceftaroline with vancomycin for the treatment of MRSA-mediated APEs in adult CF patients. The primary endpoint was the return to at least 90% of baseline lung function measured by discharge FEV1% predicted in comparison with baseline FEV1% predicted. A total of 55 patients were included in the analysis (22 receiving ceftaroline and 33 receiving vancomycin). Of the patients included in the analysis, 13 patients (59%) in theceftarolinegroup and 24 patients (73%) in the vancomycin group met the primary outcome (P=0.38). FEV1 measurements at baseline, admission and discharge were not different between treatments. Secondary outcomes including 30-day re-admission rate, 30-day mortality, treatment duration and adverse events (neutropenia, Clostridioides difficile infection and acute kidney injury) were similar between groups. Our small cohort study supports ceftaroline as an alternative treatment option for MRSA-mediated APE of CF in adults.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disordercharacterised by progressivemuscle weakness beginning in early childhood.Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis,pneumonia, or the need for ventilatory support.There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weaknessin general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase,and two trialsregistersto 23 March2021,together with reference checking, citation searching, and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria.We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane.We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC andhospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function,forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenoneon respiratory function compared to placebo. The trial that contributed numerical data includedpatientswith a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion,with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome,idebenonemay resultin less of a decline from baseline inFEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) andPEF(MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenonewas associated with fewer serious adverse events(RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) andlittle to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo.Idebenonemay result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexorsand MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacyanalysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenonemay result in slightly less of a decline in FVCandless of a decline inFEV1andPEF, but probably has little to no measurable effect on change in quality of life. Idebenoneis associated with fewer serious adverse events than placebo. Idebenonemay result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data.Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.