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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]

Background: The objective of this study was to evaluate the role of body mass index with regard to exercise performance, exercise‐induced bronchoconstriction (EIB), and respiratory symptoms in 7‐ to 16‐year‐old children. Methods: A total of 1120 outdoor running exercise challenge test results of 7‐ to 16‐year‐old children were retrospectively reviewed. Lung function was evaluated with spirometry, and exercise performance was assessed by calculating distance per 6 minutes from the running time and distance. Respiratory symptoms in the exercise challenge test were recorded, and body mass index modified for children (ISO‐BMI) was calculated for each child from height, weight, age, and gender according to the national growth references. Results: Greater ISO‐BMI and overweight were associated with poorer exercise performance (P <.001). In addition, greater ISO‐BMI was independently associated with cough (P =.002) and shortness of breath (P =.012) in the exercise challenge. However, there was no association between ISO‐BMI and EIB or with wheeze during the exercise challenge. Conclusion: Greater ISO‐BMI may have a role in poorer exercise performance and appearance of respiratory symptoms during exercise, but not in EIB in 7‐ to 16‐year‐old children. [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]

The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FENO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FENO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FENO by standard online technique. Although FENO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FENO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FENO and the severity of EIB was found ( r = 0.44, p = 0.0004), and FENO was significantly predictive of EIB. No clear association between FENO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FENO levels. However, the association between the severity of EIB and FENO is present and FENO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze. [ABSTRACT FROM AUTHOR]

Examines the role of exhaled nitric oxide in childhood asthma. Consideration of asthma as one of the most common chronic diseases of the childhood; Potential of exhaled nitric oxide and exhaled breath condensate to provide noninvasive and easily obtainable means to monitor airway inflammation; Dependence of the measured concentration of nitric oxide in exhaled air on many technical factors.

Objectives: To compare the acceptability, reproducibility, and sensitivity of spirometric outcome measures of airway caliber during challenge testing in children.Design: FEV(1), forced expiratory volume in 0.75 s, forced expiratory volume in 0.5 s, and peak expiratory flow (PEF) were recorded during stepwise dosimetric histamine challenge tests. The responses were compared, and the reproducibility at baseline and from duplicate measurements at each challenge step was determined.Patients: One hundred five children with newly diagnosed asthma, aged 5 to 10 years.Results: Compared to PEF, FEV(1) showed better baseline reproducibility (p = 0.002) and higher sensitivity (p < 0.0001) during challenge testing, determined as the change normalized to the baseline variation, while the forced expiratory volumes were not significantly different in these respects. During challenge testing in subjects with acceptable flow-volume tracings, paired recordings of FEV(1) agreed within 0.1 L in 85% and within 0.2 L in 93% of measurements. During challenge testing, the reproducibility of FEV(1) measurements was not better than that of the other indexes. Failure to exhale long enough precluded the use of FEV(1) in 16 of the children, particularly the youngest children.Conclusions: The results demonstrated that the recently published guidelines for FEV(1) measurements during challenge tests can be applied to children. During challenge tests in asthmatic children, the advantage of the shorter fractions of forced expiratory volume was that they were more often acceptably recorded than FEV(1), while they showed as good reproducibility and were also equally sensitive in assessing changes in airway obstruction. [ABSTRACT FROM AUTHOR]

Background: The use of component‐resolved allergy diagnostics has provided a clearer understanding of the species‐specific sensitization and severity of potential allergic reactions. This cross‐sectional study aimed to determine whether sensitization to allergen components in furry animals is indicative of blood eosinophilia, a positive fractional exhaled nitric oxide (FeNO) test, abnormal lung function, and asthma symptoms in children. Additionally, we investigated whether having pets during childhood affects the development of asthma or allergic sensitization to furry animals. Methods: We recruited 203 children aged 4–17 years with asthma diagnosis based on abnormal lung function and 33 controls. IgE‐sensitization to allergen components for dogs, cats, and horses was analyzed using a multiplex microarray. Children were tested with FeNO, impulse oscillometry, spirometry, methacholine challenge, and skin prick test. A questionnaire was used to investigate pet ownership and symptom profile. Results: FeNO results and blood eosinophilia revealed a correlation with sensitization to all furry animal allergens, particularly lipocalins (r = 0.203–0.560 and 0.206–0.560, respectively). Can f 3 was found to correlate with baseline R5 (r = 0.298). No association between methacholine challenge results and sensitization to furry animal allergens was found. Children with asthma who were sensitized to Can f 1, Can f 6, or both frequently reported asthma symptoms. Dog ownership was associated with a lower level of IgE‐sensitization to lipocalins, fewer asthma symptoms, and less blood eosinophilia. Conclusion: Furry animal allergen component IgE‐sensitization is a risk factor for type 2‐inflammation and asthma symptoms. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing. METHODS: This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups. RESULTS: The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen. CONCLUSIONS: Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated. [ABSTRACT FROM AUTHOR]

Variable extra thoracic obstruction has been found in spirometric studies in subjects with unilateral vocal fold paralysis. The aim of the study was to further evaluate airflow dynamics in these subjects with body plethysmography and tracheal sound analysis. Ten patients with unilateral vocal fold paralysis without a history of chronic pulmonary diseases and 10 healthy control subjects were studied. Flow-volume spirometry, body plethysmography and tracheal sound analysis were performed within 1 day. The study shows that peak inspiratory flow (PIF) and specific airway conductance (SGaw) expressed as percentage of Finnish reference values were significantly lower and airway resistance (Raw) was higher among the patients than among the controls (P=0·004, P=0·026 and P=0·004, respectively). The patients had higher sound amplitude of both inspiratory and expiratory tracheal sounds than the controls [root mean square (RMS) values of the power spectra were 31·5 and 25 dB, P=0·006 in inspiration and 31·5 and 26 dB, P=0·013 in expiration, respectively]. Quartile frequencies (F25 and F50) and RMS of expiratory tracheal sounds had significant negative correlation with PIF (P=0·02, P<0·001, P=0·02, respectively) and forced inspiratory volume in 1 s (FIV1) (P=0·01, P<0·001, P=0·01, respectively). There was also an association between F50 and peak expiratory flow (PEF) (P=0·02). According to the present study, both quiet breathing and forced inspiration are disturbed in subjects with unilateral vocal fold paralysis. A close relationship between tracheal sounds and respiratory function tests exists. [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]

Neuroendocrine cell hyperplasia of infancy (NEHI) has recently been described as an obstructive airway disease that affects infants aged 1-24 months, and presents typically with tachypnoea, crackles and hypoxia. The pathogenesis of the disease is unknown. We describe the clinical course of nine infants with radiologically and histologically confirmed NEHI. Host or environmental factors were not associated with the disease development. All infants with lung function tests demonstrated findings consistent with severe irreversible peripheral airway obstruction, assessed with whole body plethysmography (6/6) or the rapid thoracoabdominal compression technique (5/5). While the symptoms abated in all infants, six infants developed a non-atopic asthma during the follow-up. Systemic or inhaled corticosteroid treatment did not affect the duration of the symptoms. NEHI may mimic severe asthma and thus this entity should be taken into account when evaluating infants with chronic respiratory symptoms. [ABSTRACT FROM AUTHOR]

Background: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years.Methods: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit.Results: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and β agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively).Conclusions: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children. [ABSTRACT FROM AUTHOR]

Objectives: To examine the 10-year outcome of affected body surface area (BSA), respiratory symptoms, and serum IgE in adult AD patients 6 years after a 4-year intervention with topical tacrolimus. Methods: Patients who 10 years ago participated in a 4-year, open tacrolimus study ( n = 65) were contacted for assessment of affected BSA, bronchial hyper-reactivity (BHR), respiratory symptoms, skin prick tests and serum IgE. Results: Altogether, 50 (77%) patients attended the follow-up visit. The median affected BSA decreased from 19% to 1.6% during the 10-year follow-up ( p < 0.0001). Patients with active asthma and rhinitis symptoms at baseline reported a significant decrease at the follow-up ( p = 0.02 and p = 0.01). In patients with BHR at baseline, the provocative dose of inhaled histamine producing a 15% decrease in FEV1 increased. Responders (≥ 60% improvement of affected BSA) to tacrolimus treatment at the 1-year visit had a significantly smaller affected BSA at the 4- and 10-year visits than non-responders (< 60% improvement). Responders also showed a significant decrease in serum IgE at the follow-up visit compared to baseline ( p = 0.002). Conclusions: The long-term, effective treatment of patients with AD may have a beneficial effect on affected BSA, respiratory symptoms, and serum IgE. [ABSTRACT FROM AUTHOR]