Fall In FEV1 Research Articles

Exercise-induced bronchoconstriction in adolescent recreational athletes: Potential screening strategies.

Intense physical exercise in athletes increases the risk to develop exercise-induced bronchocontriction (EIB). We aimed to study EIB prevalence and explore methods for effective EIB screening. Three hundred twenty-seven adolescent athletes (12-18 years) performing at least 12 h of sports a week were included. The evaluation consisted of spirometry, eucapnic voluntary hyperpnoea test (EVH) to evaluate for EIB, FeNO, skin prick testing, blood sampling (serum markers of epithelial damage and mast cell activation), and questionnaires (AQUA©, ACT, ACQ, and exposure and symptom-related questions). Of all athletes, 22% tested positive for EIB (n = 72), 14% reported a previous asthma diagnosis and 40% were atopic. Eighty percent of EIB+ athletes did not use any inhalation therapy. EIB+ athletes were significantly younger, had decreased FEV1/FVC (%), and increased post-EVH-reversibility (%) post-salbutamol compared with EIB- athletes. Furthermore, EIB was significantly associated with previous asthma diagnosis and atopy. The best predictors for a positive EVH test were AQUA© score ≥ 6 (sensitivity of 78%, p = .0171) and wheezing during exercise (specificity of 82%, p = .0002). FeNO negatively and significantly correlated with maximal fall in FEV1 post-EVH test in atopic athletes (r = -.2735, p = .0056). Maximal fall in FEV1 was also associated with prior PM10 exposure (p = .036). Serum markers of epithelial damage were significantly associated with training type, training intensity, EIB severity, and prior air pollution exposure. Our findings support the effectiveness of a systematic respiratory screening approach, including baseline questionnaires, lung function tests, and FeNO measurement, to improve EIB detection in adolescent athletes in whom respiratory response to EVH testing is associated with prior exposure to air pollution.

Impact of Ongoing Treatment With Inhaled Corticosteroids During Specific Inhalation Challenges for Diagnosing Occupational Asthma

BackgroundSpecific inhalation challenge tests (SIC) are still the reference test for diagnosing sensitizer-induced occupational asthma (SIOA). The European Respiratory Society recommends the cessation of inhaled corticosteroids (ICS) 72h prior to SIC. ObjectiveTo assess the effect of an ongoing ICS treatment during SIC on the maximum fall in FEV1, change in methacholine PC20 as well as sputum eosinophil counts after exposure to the suspected agent. MethodsWe performed a retrospective analysis using a database of cases referred to our center for suspected SIOA from 1999 to 2022. The results of the SIC were compared between subjects treated with ICS during SIC and steroid-naïve subjects. ResultsSix-hundred and seventy-one individuals underwent SIC in the laboratory. Three hundred and eighteen were treated with ICS, whereas 353 were steroid naïve. The proportion of subjects with a positive SIC was greater among ICS treated subjects (39. 6%) compared to steroid-naïve subjects (27.5%, p<0.001). A treatment with ICS did not influence the outcome of the SIC. There was no difference in the change in PC20 or percentage of sputum eosinophils after SIC between steroid-treated and steroid-naïve subjects. ConclusionAn ongoing ICS treatment during a SIC did not affect the occurrence of an asthmatic reaction, the change in airway responsiveness or eosinophilic inflammation after exposure to the suspected agent in subjects who have been treated with ICS for a long period of time.

Assessment of lung function variability documents airflow limitation in many patients with long covid

BackgroundIt is estimated that 65 million people worldwide suffer from long covid (LC). Many LC symptoms are also reported by patients with airflow limitation, used to confirm asthma. The primary aim was to detect airflow limitation in LC patients by a methacholine bronchial provocation test (BPT) and if negative, by evaluation of diurnal variability in forced expiratory flow in 1 second (FEV1) over a two-weeks’ period. The second aim was to assess responsiveness to asthma treatment on diurnal FEV1 variability and LC symptoms. MethodsPatients with LC for at least six months were recruited in this open diagnostic study. Burden of LC symptoms were reported on a 10-point Likert scale (0 = not troubled, 10 = extremely troubled) at inclusion and after three weeks’ asthma treatment. A positive methacholine BPT was defined by an accumulated provocation dose (PD20)<8 μmol causing 20% fall in FEV1. App-based spirometer was used for diurnal FEV1 variability, deemed positive by diurnalvariability in FEV1 ≥12%. ResultsAirflow limitation was documented by positive methacholine BPT in 8/30 (27%), or by excessive diurnal variability in FEV1 in 21/22 (95%) of the BPT negative LC patients. One patient dropped out due to personal issues. Three weeks’ asthma treatment normalised mean diurnal FEV1 variability from 18.0% to 7.3%, p < 0.001. Significant reductions were observed for fatigue and dyspnoea, from 8.3 to 6.1, p < 0.001, and 3.0 to 0, p < 0.001, respectively. ConclusionThis study indicate that airflow limitation may be detected in many LC patients if evaluation of diurnal variability in FEV1 is included in the diagnostics.

MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction.

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma's pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR.

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.

Is there cardiac autonomic dysfunction in children and adolescents with exercise-induced bronchospasm?

ABSTRACT Background The pulmonary impairment in patients with bronchoconstriction induced by eucapnic voluntary hyperpnea(EVH) goes beyond the respiratory system, also impairing autonomic nervous modulation. This study aimed to evaluate the behavior of cardiac autonomic modulation in young asthmatics with and without EIB after the EVH test. Research design and methods A cross-sectional study design using 54 asthmatics(51.9% female), aged between 10 and 19 years, investigated with the EVH test. Forced expiratory volume in one second(FEV1) was measured at 5, 10, 15, and 30 min after EVH. Heart rate variability(HRV) measures of time were assessed pre and 30 min-post EVH. The diagnosis of Exercise-Induced bronchoconstriction with underlying clinical asthma(EIBA) was confirmed by a fall in FEV1 ≥10% compared to baseline. Results Thirty(55.5%) asthmatics had EIBA. Subjects with EIBA have reduced mean of the R-R intervals in relation to baseline until 15 minutes after EVH. Individuals without EIBA had increased parasympathetic activity compared to baseline(rMSSD) from 5 min after EVH(p < 0.05). This parasympathetic activity increase in relation to baseline was seen in individuals with EIBA after 25 minutes (rMSSD = 49.9 ± 5.3 vs 63.5 ± 7.2, p < 0.05). Conclusion Young asthmatics with EIBA present a delay in the increase of the parasympathetic component after EVH when compared to asthmatics without EIBA.

Fractional exhaled nitric oxide in the assessment of exercise-induced bronchoconstriction: A multicenter retrospective analysis of UK-based athletes.

Exercise-induced bronchoconstriction (EIB) is not only highly prevalent in people with asthma, but can also occur independently, particularly in athletes. Fractional exhaled nitric oxide (FeNO) is an indirect biomarker of type 2 airway inflammation that has an established role in the assessment and management of asthma. The aim was to evaluate the value of FeNO in the assessment of EIB in athletes. Multicenter retrospective analysis. In total, 488 athletes (male: 76%) performed baseline FeNO, and spirometry pre- and post-indirect bronchial provocation via eucapnic voluntary hyperpnea (EVH). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for established FeNO thresholds-that is, intermediate (≥25 ppb) and high FeNO (≥40 ppb and ≥ 50 ppb)-and were evaluated against objective evidence of EIB (≥10% fall in FEV1 ). The diagnostic accuracy of FeNO was calculated using receiver operating characteristics area under the curve (ROC-AUC). Thirty-nine percent of the athletes had a post-EVH fall in FEV1 consistent with EIB. FeNO values ≥25 ppb, ≥40 ppb, and ≥ 50 ppb were observed in 42%, 23%, and 17% of the cohort, respectively. The sensitivity of FeNO ≥25 ppb was 55%, which decreased to 37% and 27% at ≥40 ppb and ≥ 50 ppb, respectively. The specificity of FeNO ≥25 ppb, ≥40 ppb, and ≥ 50 ppb was 66%, 86%, and 89%, respectively. The ROC-AUC for FeNO was 0.656. FeNO ≥40 ppb provides good specificity, that is, the ability to rule-in a diagnosis of EIB. However, due to the poor sensitivity and predictive values, FeNO should not be employed as a replacement for indirect bronchial provocation in athletes.

Can development of asthma and bronchial hyperreactivity be reduced by subcutaneous immunotherapy in adult patients with allergic rhinitis?

Allergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis. The retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment. A total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled.Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30-35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046). In our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma developmen.

Development and validation of a predictive model combining patient-reported outcome measures, spirometry and exhaled nitric oxide fraction for asthma diagnosis.

Although asthma is a common disease, its diagnosis remains a challenge in clinical practice with both over- and underdiagnosis. Here, we performed a prospective observational study investigating the value of symptom intensity scales alone or combined with spirometry and exhaled nitric oxide fraction (F ENO) to aid in asthma diagnosis. Over a 38-month period we recruited 303 untreated patients complaining of symptoms suggestive of asthma (wheezing, dyspnoea, cough, sputum production and chest tightness). The whole cohort was split into a training cohort (n=166) for patients recruited during odd months and a validation cohort (n=137) for patients recruited during even months. Asthma was diagnosed either by a positive reversibility test (≥12% and ≥200 mL in forced expiratory volume in 1 s (FEV1)) and/or a positive bronchial challenge test (provocative concentration of methacholine causing a 20% fall in FEV1 ≤8 mg·mL-1). In order to assess the diagnostic performance of symptoms, spirometric indices and F ENO, we performed receiver operating characteristic curve analysis and multivariable logistic regression to identify the independent factors associated with asthma in the training cohort. Then, the derived predictive models were applied to the validation cohort. 63% of patients in the derivation cohort and 58% of patients in the validation cohort were diagnosed as being asthmatic. After logistic regression, wheezing was the only symptom to be significantly associated with asthma. Similarly, FEV1 (% pred), FEV1/forced vital capacity (%) and F ENO were significantly associated with asthma. A predictive model combining these four parameters yielded an area under the curve of 0.76 (95% CI 0.66-0.84) in the training cohort and 0.73 (95% CI 0.65-0.82) when applied to the validation cohort. Combining a wheezing intensity scale with spirometry and F ENO may help in improving asthma diagnosis accuracy in clinical practice.

Bronchial hyperresponsiveness and asthma during oral immunotherapy for egg or peanut allergy in children.

BackgroundBronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control.MethodsMethacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double‐blind, placebo‐controlled food challenge and 80 control children without food allergy. Of the 89 food‐allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6–12 months of OIT.ResultsMethacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut‐allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome.ConclusionBHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.

Can the response to a single dose of beclomethasone dipropionate predict the outcome of long-term treatment inchildhood exercise-induced bronchoconstriction?

Exercise-induced bronchoconstriction (EIB) is a frequent and highly specific symptom of childhood asthma. Inhaled corticosteroids (ICS) are the mainstay of controller therapy for EIB and asthma; however, a proportion of asthmatic children and adolescents is less responsive to ICS. We hypothesized that a single dose response to ICS could function as a predictor for individual long-term efficacy of ICS. To assess the predictive value of the bronchoprotective effect of a single-dose beclomethasone dipropionate (BDP) against EIB for the bronchoprotective effect of 4weeks of treatment, using an exercise challenge test (ECT). Thirty-two steroid-naïve children and adolescents aged 6 to 18years with EIB were included in this prospective cohort study. They performed an ECT at baseline, after a single-dose BDP (200µg) and after 4weeks of BDP treatment (100µg twice daily) to assess EIB severity. The response to a single-dose BDP on exercise-induced fall in FEV1showed a significant correlation with the response on exercise-induced fall in FEV1 after 4weeks of BDP treatment (r=.38, p=.004). A reduction in post-exercise fall in FEV1 of more than 8% after a single-dose BDP could predict BDP efficacy against EIB after 4weeks of treatment with a positive predictive value of 100% (CI: 86.1-100%) and a negative predictive value of 29.4% (CI: 11.7%-53.7%). We found that the individual response to a single-dose BDP against EIB has a predictive value for the efficacy of long-term treatment with BDP. This could support clinicians in providing personalized management of EIB in childhood asthma.

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.

Cut-off value for exercise-induced bronchoconstriction based on the features of the airway obstruction.

The current cut-off value for diagnosing exercise-induced bronchoconstriction (EIB) in adults—percent fall in FEV1 (ΔFEV1) ≥ 10% after exercise challenge test (ECT)—has low specificity and weak evidences. Therefore, this study aimed to identify the cut-off value for EIB that provides the highest diagnostic sensitivity and specificity. Participants who underwent the ECT between 2007 and 2018 were categorized according to ΔFEV1: definite EIB (ΔFEV1 ≥ 15%), borderline (10% ≤ ΔFEV1 < 15%), and normal (ΔFEV1 < 10%). Distinct characteristics of the definite EIB group were identified and explored in the borderline EIB group. A receiver operating characteristic curve was plotted to determine the optimal cut-off value. Of 128 patients, 60 were grouped as the definite EIB group, 23 as the borderline group, and 45 as the normal group. All participants were men, with a median age of 20 years (interquartile range [IQR:] 19–23 years). The definite EIB group exhibited wheezing on auscultation (P < 0.001), ΔFEV1/FVC ≥ 10% (P < 0.001), and ΔFEF25–75% ≥ 25% (P < 0.001) compared to other groups. Eight (8/23, 34.8%) patients in the borderline group had at least one of these features, but the trend was more similar to that of the normal group than the definite EIB group. A cut-off value of ΔFEV1 ≥ 13.5% had a sensitivity of 98.5% and specificity of 93.5% for EIB. Wheezing on auscultation, ΔFEV1/FVC ≥ 10%, and ΔFEF25–75% ≥ 25% after ECT may be useful for the diagnosis of EIB, particularly in individuals with a ΔFEV1 of 10–15%. For EIB, a higher cut-off value, possibly ΔFEV1 ≥ 13.5%, should be considered as the diagnostic criterion.

Exacerbation Profile and Risk Factors in a Type-2-Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes.

Rationale: The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a minority of patients with severe asthma, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. Objectives: The objective of this study was to explore the differences between study exacerbators and nonexacerbators, to describe physiological changes at exacerbation in those who are T2HIGH and T2LOW at the time of exacerbation, and to evaluate the stability of inflammatory phenotypes when stable and at exacerbation. Methods: Exacerbation assessment was a prespecified secondary analysis of data from a 48-week, multicenter, randomized controlled clinical study comparing the use of biomarkers and symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW (fractional exhaled nitric oxide ⩽ 20 ppb and blood eosinophil count ⩽ 150 cells/µl) or T2HIGH (fractional exhaled nitric oxide > 20 or blood eosinophil count > 150) at study enrollment and at each exacerbation. Here, we report the findings of the exacerbation analyses, including comparison of exacerbators and nonexacerbators, the physiological changes at exacerbation in those who had evidence of T2 biology at exacerbation versus those that did not, and the stability of inflammatory phenotypes when stable and at exacerbation. Measurements and Main Results: Of the 301 participants, 60.8% (183) had one or more self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher body mass index, and have more exacerbations requiring oral corticosteroid and unscheduled primary care attendances for exacerbations. At enrollment, 23.6% (71) were T2LOW and 76.4% (230) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU (high dependency unit)/ICU and to be receiving maintenance oral corticosteroids. At exacerbation, the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function (mean fall in T2LOW FEV1, 200 [400] ml vs. T2HIGH 200 [300] ml; P = 0.93) and symptom increase (ACQ5: T2LOW, 1.4 [0.8] vs. T2HIGH, 1.3 [0.8]; P = 0.72), with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations. The inflammatory phenotype within individual patients was dynamic; inflammatory phenotype at study entry did not have a significant association with exacerbation phenotype. Conclusions: Asthma exacerbations demonstrating a T2LOW phenotype were physiologically and symptomatically similar to T2HIGH exacerbations. T2LOW asthma was an unstable phenotype, suggesting that exacerbation phenotyping should occur at the time of exacerbation. The clinically significant exacerbations in participants without evidence of T2 biology at the time of exacerbation highlight the unmet and pressing need to further understand the mechanisms at play in non-T2 asthma. Clinical trial registered with www.clinicaltrials.gov (NCT02717689).

Relapse of Sarcoidosis After Lung Transplantation

<h3>Introduction</h3> Sarcoidosis is a systemic granulomatous disease of unknown etiology. It most commonly affects the lungs, lymph nodes and skin, but the eyes, liver, heart and central nervous system can also be involved. Lung involvement is present in almost all patients with sarcoidosis. Prognosis is generally benign with more than half of patients entering spontaneous remission. However, a third of patients exhibit progressive disease culminating in organ dysfunction. Although sarcoidosis is not among the most frequent causes for lung transplantation, this can be the only therapeutic alternative in this subset of patients. <h3>Case Report</h3> The authors present the case of a 48-year-old caucasian male patient, with no relevant medical history, who had been diagnosed with sarcoidosis since 2006. Thoracic lymph nodes and lung parenchyma were affected on presentation, and screening showed ocular involvement as well. The patient experienced a flare in 2015, with worsened dyspnea and decline in FEV1 and DLCO values, and was started on prednisolone and methotrexate. Clinical stability for the next three years allowed suspension of methotrexate in 2018, while maintaining low dose steroids. However, new clinical and functional decline, as well as detection of cardiac involvement, prompted a six month course of infliximab in 2019. Due to continued worsening of lung function tests (LFTs) and progression to lung fibrosis, the patient underwent bilateral lung transplantation in June 2020 without major complications, and was discharged a month later. He remained asymptomatic and follow-up LFTs were stable until February 2021, eight months after the transplant, when a new fall in FEV1 was noticed. Flexible bronchoscopy and transbronchial biopsies (TBB) were performed, revealing minimal acute rejection (A1) and granulomas compatible with sarcoidosis. Methylprednisolone pulse therapy was administered, followed by weaning. FEV1 levels improved in subsequent evaluations, although TBB performed three months later continued to show signs of sarcoidosis. <h3>Summary</h3> Allograft relapse of sarcoidosis is relatively common - Schultz et al have reported a recurrence rate of 30%. Research by Ionescu et al has showed the granulomas originate from the recipient. Recurrence of sarcoidosis does not seem to impact survival or lung function of lung transplant recipients. This case illustrates coexistence of both acute rejection and recurrent sarcoidosis.

Extracorporeal Photopheresis in Lung Transplantation - New Frontiers in Infection Immunomodulation - A Case Series

<h3>Purpose</h3> Lung transplantation outcomes are limited by chronic lung allograft dysfunction (CLAD). Infection driven loss of graft function is a common cause of CLAD. Extracorporeal photopheresis (ECP) is a salvage therapy post lung transplantation with the indications broadening as experience and availability increases. The therapeutic role of ECP is yet to be explored in infection driven CLAD. <h3>Methods</h3> A retrospective audit of all lung transplant recipients at a single UK lung transplant centre who received ECP from 2017 to 2021 was performed using electronic records.5 patients with infection driven CLAD treated with ECP were identified. <h3>Results</h3> 40% were male with median(range) age 63(30-70) years. Median duration from lung transplant to ECP was 38(13-53)months and median duration of ECP was 14(10-15) months. All 5 patients were responders at 2 months (defined as less than 20 percent FEV1 fall). Median(range) FEV1 percentage change improved from -17% (-20 to+10%) one year pre-ECP to +1%(-1to+10%) one year post-ECP (Figure1). Mycophenolate mofetil was stopped for all patients on initiation of ECP. 4 patients had a reduction in length of stay in hospital (Figure 2). 3 patients were alive 1 year post ECP whilst 2 patients are still within their first year of follow up. <h3>Conclusion</h3> ECP can help to stabilize graft function in lung transplant recipients with recurrent infections. It allows for modification of conventional immunosuppression regimens and contributes to improved quality of life by decreasing the length of hospital stay and number of antibiotic days.

Deprescribing montelukast in children with asthma: a systematic review

BackgroundNational and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP).ObjectiveTo...

Albuterol/budesonide for the treatment of exercise-induced bronchoconstriction in patients with asthma: The TYREE study

BackgroundPT027 is a fixed-dose combination of albuterol (salbutamol) and budesonide in a single pressurized metered-dose inhaler. ObjectiveTo evaluate the efficacy and safety of albuterol/budesonide compared with placebo in patients with asthma and exercise-induced bronchoconstriction (EIB). MethodsIn this randomized, double-blind, 2-period, single-dose crossover study, adolescents and adults with asthma and EIB (defined by ≥20% decrease from pre-exercise challenge forced expiratory volume in 1 second [FEV1]) were randomized to albuterol/budesonide (180/160 µg) followed by placebo (n = 29) or the reverse sequence (n = 31). Subjects were stratified by background therapy (as-needed short-acting β2-agonist alone or low-to-medium dose inhaled corticosteroid plus as-needed short-acting β2-agonist). FEV1 was measured 5 minutes pre-dose, 30 minutes postdose (5 minutes pre-exercise challenge [baseline]), and 5, 10, 15, 30, and 60 minutes postexercise. The primary end point was maximum percentage fall from baseline in FEV1 up to 60 minutes postexercise challenge. ResultsLeast squares mean maximum percentage fall in FEV1 up to 60 minutes postexercise challenge was 5.45% with albuterol/budesonide vs 18.97% with placebo (difference, −13.51% [95% confidence interval, −16.94% to −10.09%]; P < .001). More subjects were fully protected (maximum percentage fall in FEV1 post-exercise challenge < 10%) with albuterol/budesonide than with placebo (78.3% vs 28.3%; P < .001). The treatment effect was consistent irrespective of background inhaled corticosteroid therapy, and albuterol/budesonide was well tolerated. ConclusionIn adolescents and adults with asthma and EIB, a single dose of albuterol/budesonide 180/160 µg taken approximately 30 minutes before exercise was significantly more effective than placebo in preventing EIB. Trial RegistrationClinicalTrials.gov Identifier: NCT04234464

Anti–Interleukin-5 Therapy Is Associated with Attenuated Lung Function Decline in Severe Eosinophilic Asthma Patients From the Belgian Severe Asthma Registry

Asthmatics have accelerated lung function decline over time compared with healthy individuals. To evaluate risk factors for accelerated lung function decline. In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of post-bronchodilation forced expiratory volume in 1 s [FEV1] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV1 decline. In the overall population (n= 318), median annual FEV1 decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV1) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV1 decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV1 were associated with accelerated FEV1 decline. Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV1 decline. The causality of this observation should, however, be confirmed in future prospective controlled studies.

Filamentous fungi in the airway of patients with cystic fibrosis: Just spectators?

BackgroundThere are important advances in the management of bacterial infection in patients with cystic fibrosis (CF), but there are many gaps in the field of fungal infections. AimsThe aim of this study was to analyse whether chronic respiratory filamentous fungal colonization had clinical impact and whether antifungal treatment can change the disease. MethodsThe prospective, bicentric and descriptive study was carried out within a 3-year follow-up period, with four-month periodicity medical controls. Adult patients from two CF units of tertiary hospitals were included. Clinical, microbiological, analytical and spirometric variables were collected. Quality of life was evaluated in a subgroup, using the Spanish version of the Revised Cystic Fibrosis Quality of Life Questionnaire (CFQ-R). To statistically analyze the evolution of forced expiratory along time (volume of air blown out in 1 second -FEV1-) and the forced vital capacity (FVC), mixed linear models were carried out. ResultsFrom the ninety-eight patients under study, 40 suffered chronic filamentous fungal colonization. The presence of filamentous fungi in airway was associated to an annual fall of FEV1 and FVC of 0.029 and 0.017 litres, respectively (p<0.001). In addition, worse quality of life based on CFQ-R, significant when concerning physical condition and emotional state, was also linked with the fungal colonization. Protocolized antifungal therapy, nebulized or oral, improved FEV1 in 0.023 and 0.024 litres per year, respectively (p<0.001). ConclusionsChronic filamentous fungal colonization in patients with CF is associated with a significant annual decline of lung function that persists over time. Chronic antifungal therapy slows down this progression, mainly in the patient with more advanced disease.