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A systematic review was performed to determine if the continuous laryngoscopy exercise test (CLE) has been used in the diagnostics of exercise dyspnea in adults with asthma, and whether inducible laryngeal obstruction (ILO) is found in those with asthma or with severe or difficult-to-treat asthma. We used Scopus and PubMed databases. The articles published up to 13 August 2019 were considered. We excluded manuscripts that did not contain information about adult patients with asthma. We included six studies from 59 search results in Scopus and none from the 17 search results in PubMed. The articles included 455 study individuals. Of these, 229 (50.3%) had diagnosed asthma or were treated with asthma medication. Altogether 31/229 (13.5%) subjects with diagnosis of asthma or previous asthma treatment had exercise-induced laryngeal obstruction (EILO) as comorbidity. The CLE test was performed on 229 patients with asthma. The method was used only for differential diagnosis of exercise-induced dyspnea to confirm EILO. At least 10/455 (2.2%) out of the 455 subjects experienced adverse events. This systematic review revealed that only a small proportion of patients with asthma had undergone the CLE test to assess exercise-induced dyspnea. None of the selected manuscripts reported severity of asthma. Whether CLE provides a valuable diagnostic tool for patients with severe or difficult-to-treat asthma cannot be determined according to this review. [ABSTRACT FROM AUTHOR]

Fractional exhaled nitric oxide (FENO) is used to assess eosinophilic inflammation of the airways. FENO values are influenced by the expiratory flow rate and orally produced NO. We measured FENO at four different expiratory flow levels after two different mouthwashes: tap water and carbonated water. Further, we compared the alveolar NO concentration (CANO), maximum airway NO flux (J'awNO) and airway NO diffusion (DawNO) after these two mouthwashes. FENO was measured in 30 volunteers (healthy or asthmatic) with a chemiluminescence NO-analyser at flow rates of 30, 50, 100 and 300 mL/s. A mouthwash was performed before the measurement at every flow rate. The carbonated water mouthwash significantly reduced FENO compared to the tap water mouthwash at all expiratory flows: 50 mL/s (p < .001), 30 mL/s (p = .001), 100 mL/s (p < .001) and 300 mL/s (p = .004). J'awNO was also significantly reduced (p = .017), however, there were no significant differences in CANO and DawNO. In conclusion, a carbonated water mouthwash can significantly reduce oropharyngeal NO compared to a tap water mouthwash at expiratory flows of 30-300 mL/s without affecting the CANO and DawNO. Therefore, mouthwashes need to be taken into account when comparing FENO results. [ABSTRACT FROM AUTHOR]

Background: The Easyhaler® (EH) device-metered dry powder inhaler containing budesonide and formoterol is being developed for asthma and chronic obstructive pulmonary disease (COPD). As a part of product optimization, a series of in vitro and in vivo studies on flow rate dependency were carried out. Methods: Inspiratory flow parameters via EH and Symbicort® Turbuhaler® (TH) inhalers were evaluated in 187 patients with asthma and COPD. The 10th, 50th, and 90th percentile flow rates achieved by patients were utilized to study in vitro flow rate dependency of budesonide/formoterol EH and Symbicort TH. In addition, an exploratory pharmacokinetic study on pulmonary deposition of active substances for budesonide/formoterol EH in healthy volunteers was performed. Results: Mean inspiratory flow rates through EH were 64 and 56 L/min in asthmatics and COPD patients, and through TH 79 and 72 L/min, respectively. Children with asthma had marginally lower PIF values than the adults. The inspiratory volumes were similar in all groups between the inhalers. Using weighted 10th, 50th, and 90th percentile flows the in vitro delivered doses (DDs) and fine particle doses (FPDs) for EH were rather independent of flow as 98% of the median flow DDs and 89%-93% of FPDs were delivered already at 10th percentile air flow. Using±15% limits, EH and TH had similar flow rate dependency profiles between 10th and 90th percentile flows. The pharmacokinetic study with budesonide/formoterol EH in healthy subjects ( n=16) revealed a trend for a flow-dependent increase in lung deposition for both budesonide and formoterol. Conclusions: Comparable in vitro flow rate dependency between budesonide/formoterol EH and Symbicort TH was found using the range of clinically relevant flow rates. The results of the pharmacokinetic study were in accordance with the in vitro results showing only a trend of flow rate-dependant increase in lung deposition of active substances with EH. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether patients of varying ages and lung function with asthma or those with chronic obstructive pulmonary disease (COPD) can achieve sufficient inspiratory flows for effective use of the fixed-dose combination of salmeterol-fluticasone propionate and budesonide-formoterol dispensed with the Easyhaler ® (EH) device-metered, multi-dose dry powder inhaler (DPI)., Methods: A pooled analysis of two randomized, multicenter, crossover, open-label studies (NCT01424137; NCT009849061) was conducted to characterize inspiratory flow parameters across the EH, Seretide Diskus (DI) and Symbicort Turbuhaler (TH) inhalers in patients with asthma and/or COPD of varying severity. The primary endpoint was peak inspiratory flow (PIF) rate through the EH., Results: The intent-to-treat population comprised 397 patients; 383 patients were included in the per-protocol (PP) population. The mean PIF (standard deviation) values through the EH in patients <18 and ≥18 years of age with asthma and in those with COPD, were similar: 61.4 (11.5), 69.7 (13.5), and 61.9 (13.2) L/min, respectively. These flow rates correspond to pressure drops of 5.05 (1.80), 6.52 (2.34) and 5.19 (2.07) kPa, respectively. In total, 380 (99.2%) of patients in the PP population were able to generate a PIF rate through the EH of ≥30 L/min, which is required to enable consistent dose delivery from the DPI; there was a moderate direct association between age and PIF in younger patients with asthma, but this was inverse and less apparent in adult patients with asthma and/or those with COPD. Height and weight were also moderately correlated with PIF. Stronger associations with PIF were observed for some lung function parameters, particularly native PIF and forced inspiratory vital capacity., Conclusions: Over 99% of patients with asthma and/or COPD were able to inhale through the EH with an adequate PIF rate, irrespective of age, or severity of airway obstruction. This confirms that patients with asthma and/or COPD can achieve inspiratory flows via the EH DPI that are sufficient for its effective use., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2112). LPM reports personal fees from Orion Pharma, AstraZeneca and Chiesi, all outside the submitted work. ASP reports personal fees from Orion Pharma, outside of the submitted work. VV, SL and MV are employees of Orion Corporation, Orion Pharma. RJ reports personal fees from Orion Pharma (outside of the submitted work), Novartis, Boehringer and GSK outside the submitted work., (2021 Journal of Thoracic Disease. All rights reserved.)

Fractional exhaled nitric oxide (F ENO ) is used to assess eosinophilic inflammation of the airways. F ENO values are influenced by the expiratory flow rate and orally produced NO. We measured F ENO at four different expiratory flow levels after two different mouthwashes: tap water and carbonated water. Further, we compared the alveolar NO concentration (C ANO ), maximum airway NO flux (J' awNO ) and airway NO diffusion (D awNO ) after these two mouthwashes. F ENO was measured in 30 volunteers (healthy or asthmatic) with a chemiluminescence NO-analyser at flow rates of 30, 50, 100 and 300 mL/s. A mouthwash was performed before the measurement at every flow rate. The carbonated water mouthwash significantly reduced F ENO compared to the tap water mouthwash at all expiratory flows: 50 mL/s (p < .001), 30 mL/s (p = .001), 100 mL/s (p < .001) and 300 mL/s (p = .004). J' awNO was also significantly reduced (p = .017), however, there were no significant differences in C ANO and D awNO . In conclusion, a carbonated water mouthwash can significantly reduce oropharyngeal NO compared to a tap water mouthwash at expiratory flows of 30-300 mL/s without affecting the C ANO and D awNO . Therefore, mouthwashes need to be taken into account when comparing F ENO results.

Lung function variability is a fundamental feature of asthma but has been difficult to quantify in children due to methodological limitations. We assessed the feasibility and clinical implications of overnight flow variability measurement at home using impedance pneumography in young children.44 children aged 3-7 years with recurrent or persistent lower airway symptoms were recruited. Patients were divided into high- or lower-risk groups (HR and LR groups) based on their risk of asthma (modified Asthma Predictive Index), and a third group was formed of children who had a history of wheeze and who were treated with inhaled corticosteroids (ICS group). Tidal volume and the derived flow were recorded through skin electrodes using impedance pneumography at home during sleep. Quantities describing overnight change in expiratory flow-volume minimum curve shape correlation (CSRmin) and respiratory chaoticity (minimum noise limit (NLmin)) were derived.Recordings were successful in 34 children. CSRmin differed between the HR and LR groups (p=0.002) and between the HR and ICS groups (p=0.003), indicating a stronger change in flow profile shape in the HR group. NLmin differed between the HR and LR groups (p=0.014), indicating momentarily lowered chaoticity in the HR group.Impedance pneumography was found feasible for quantifying nocturnal lung function variability and the measured variability was associated with risk of asthma in young children., (Copyright ©ERS 2016.)

Background: Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies., Methods: Thirty-nine infants (median age 0.9 years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies., Results: The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1β, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine., Conclusions: A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.