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International Journal of Occupational... Mar 2020Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing...
OBJECTIVES
Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms.
MATERIAL AND METHODS
Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed.
RESULTS
Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol.
CONCLUSIONS
The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.
Topics: Adult; Allergens; Asthma, Occupational; Bronchial Provocation Tests; Female; Humans; Male; Mannitol; Methacholine Chloride; Middle Aged; Single-Blind Method
PubMed: 32080681
DOI: 10.13075/ijomeh.1896.01459 -
International Archives of Allergy and... 2020Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via...
INTRODUCTION
Bronchoconstriction was recently shown to cause airway remodeling and induce allergic airway inflammation in asthma. However, the mechanisms how mechanical stress via bronchoconstriction could induce airway inflammation and remodeling remain unclear.
OBJECTIVE
We investigated the effect of bronchoconstriction induced by methacholine inhalation in a murine model of asthma.
METHODS
BALB/c female mice were sensitized and challenged with ovalbumin (OVA), followed by treatment with methacholine by a nebulizer twice a day for 7 days. Twenty-four hours after the last methacholine treatment, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The BALF was analyzed for total and differential cell counts and cytokine levels. The lung tissues were analyzed for goblet cell metaplasia, thickness of the smooth muscle, and lung fibrosis. The expression of cytokines in the lung was also examined.
RESULTS
OVA sensitization and challenge induced infiltration of total cells, macrophages, and eosinophils in the BALF along with goblet cell metaplasia and increased airway smooth muscle hypertrophy. Seven days after the last OVA challenge, untreated mice achieved reduction in airway inflammation, while methacholine maintained the number of BALF total cells, macrophages, and eosinophils. The percentage of goblet cells and the thickness of airway smooth muscle were also maintained by methacholine. Moreover, the treatment of methacholine induced the expression of transforming growth factor (TGF)-β in the lung. This result indicates that the production of TGF-β is involved in induction of airway remodeling caused by bronchoconstriction with methacholine.
CONCLUSIONS
Repeated bronchoconstriction caused by methacholine inhalation elicited allergic airway inflammation and airway remodeling.
Topics: Administration, Inhalation; Allergens; Animals; Asthma; Bronchoconstriction; Disease Models, Animal; Eosinophils; Female; Humans; Lung; Macrophages; Methacholine Chloride; Mice; Mice, Inbred BALB C; Ovalbumin; Transforming Growth Factor beta
PubMed: 32791506
DOI: 10.1159/000509606 -
Occupational Medicine (Oxford, England) Feb 2022Firefighter applicants (FFAs) with a history of asthma may be refused entry to the fire service because of potentially putting themselves and others at risk.
BACKGROUND
Firefighter applicants (FFAs) with a history of asthma may be refused entry to the fire service because of potentially putting themselves and others at risk.
AIMS
We undertook a service evaluation to identify respiratory and employment outcomes of FFAs with a history of asthma who had undergone additional respiratory assessment at our specialist occupational lung disease clinic during 2005-19.
METHODS
We reviewed FFA medical records and categorized them as having either no current asthma or definite/probable asthma at the time of clinic assessment. 'No current asthma' was defined as negative non-specific bronchial hyper-responsiveness (BHR) to histamine/methacholine, and no symptoms or treatment within the 2 years before clinic. 'Definite/probable current asthma' was defined as either positive BHR, or negative BHR with symptoms and/or treatment within the previous 2 years. Around 1 year later, we contacted FFAs to enquire about their application outcome and current respiratory symptoms.
RESULTS
Data were available on 116 applicants; of whom, 45% (n = 52) had definite/probable current asthma and were significantly more likely to be older, atopic to common aeroallergens, report atopic disease and have a lower forced expiratory volume in one second/forced vital capacity ratio compared with applicants with no current asthma. Only two individuals' applications were rejected due to asthma. At follow-up, just 2 (2%) of the 90 operational firefighters reported any recent trouble with asthma.
CONCLUSIONS
A history of asthma alone is not sufficient to determine current asthma in FFAs. Even with a diagnosis of current asthma, FFAs are mostly successful in their application to join the fire service.
Topics: Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Firefighters; Forced Expiratory Volume; Humans; Methacholine Chloride
PubMed: 34919722
DOI: 10.1093/occmed/kqab162 -
Pediatric Pulmonology Sep 2017The long-term respiratory characteristics of ex-preterm children with bronchopulmonary dysplasia (BPD) are not established. The objective of this study was to describe... (Comparative Study)
Comparative Study
BACKGROUND
The long-term respiratory characteristics of ex-preterm children with bronchopulmonary dysplasia (BPD) are not established. The objective of this study was to describe hallmarks of BPD at school age in comparison to children with atopic asthma.
METHODS
This study was a cross-sectional descriptive comparative study in a hospital-based setting. Thirty schoolchildren diagnosed with BPD (10.4 years/born at 26.6 weeks' gestation) and 30 age- and sex-matched children with asthma and sensitized to airborne allergens (IgE >0.35 kU /L) were analyzed. Measurements included fraction of exhaled nitric oxide (FENO, ppb), dynamic and static lung function, and bronchial provocation with methacholine (PD:20) and mannitol (PD:15), as well as an evaluation of respiratory symptoms using the asthma control test (C-ACT).
RESULTS
Lung function measures (FEV1% 77 vs 84, FEV1/FVC% 85 vs 91, FEF50% 61 vs 80) and carbon monoxide diffusion capacity (DLCO%, 81 vs 88) were all reduced in children with BPD compared to asthma (P values <0.042). FENO values were also significantly lower in children with BPD (12 vs 23, P = 0.019). The proportion of positive methacholine tests (74% vs 93%, P = 0.14) was comparable between BPD and asthma. However, less responsiveness towards mannitol (19% vs 61%, P = 0.007) and fewer self-reported symptoms (C-ACT, median 26 vs 24, P = 0.003) were found in the BPD group.
CONCLUSION
Respiratory hallmarks of BPD at school-age were reduced lung function, limited responsiveness towards indirectly acting mannitol but hyper-responsiveness towards direct acting methacholine and impairment in diffusion capacity. Children with BPD displayed less evidence of airway inflammation compared with atopic asthma.
Topics: Allergens; Asthma; Bronchi; Bronchial Provocation Tests; Bronchopulmonary Dysplasia; Carbon Monoxide; Child; Cross-Sectional Studies; Exhalation; Female; Humans; Immunoglobulin E; Male; Methacholine Chloride; Nitric Oxide; Respiratory Function Tests
PubMed: 28636794
DOI: 10.1002/ppul.23741 -
Pulmonary Pharmacology & Therapeutics Feb 2015Mice with Plp1 gene duplication model the most common form of Pelizaeus-Merzbacher disease (PMD), a CNS disease in which patients may suffer respiratory complications....
Mice with Plp1 gene duplication model the most common form of Pelizaeus-Merzbacher disease (PMD), a CNS disease in which patients may suffer respiratory complications. We hypothesized that affected mice would lack airway responsiveness compared to wild-type and carrier mice during methacholine challenge. Wild-type (n = 10), carrier female (n = 6) and affected male (n = 8) mice were anesthetized-paralyzed, tracheostomized and ventilated. Respiratory mechanics were recorded at baseline and during escalating doses of nebulized methacholine followed by albuterol. Lung resistance (RL) was the primary endpoint. Lung tissues were assayed for inflammatory and histological differences. At baseline, phase angles were higher in carrier and affected mice than wild-type. Dose-response RL curves in affected and carrier mice indicated a lack of methacholine response. Albuterol reduced RL in wild-type and carrier, but not affected mice. Affected mice exhibited lower interleukin (IL)-6 tissue levels and alveolar inflammatory infiltrates. Affected and carrier mice, compared to wild-type, lacked airway reactivity during methacholine challenge, but only affected mice exhibited decreased lung tissue levels of IL-6 and inflammation.
Topics: Albuterol; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gene Duplication; Interleukin-6; Male; Methacholine Chloride; Mice; Myelin Proteolipid Protein; Pelizaeus-Merzbacher Disease; Pneumonia; Respiratory Mechanics
PubMed: 25445931
DOI: 10.1016/j.pupt.2014.10.004 -
Automated, high temporal resolution mechanics measurements during incubation of contractile tissues.Journal of Biomechanics May 2023Muscle tissue mechanics and contractility measurements have a great advantage over cultured cell level experiments as their mechanical and contractile properties are...
Muscle tissue mechanics and contractility measurements have a great advantage over cultured cell level experiments as their mechanical and contractile properties are much closer to in vivo tissue properties. However, tissue level experiments cannot be combined with incubation with the same time resolution and consistency as cell culture studies. Here we present a system in which contractile tissues can be incubated for days while intermittently being tested for their mechanical and contractile properties. A two-chamber system was developed with control of temperature in the outer chamber and CO and humidity control in the inner, sterile chamber. Incubation medium, to which biologically active components may be added, is reused after each mechanics test to preserve both added and released components. Mechanics and contractility are measured in a different medium to which, through a high accuracy syringe pump, up to 6 different agonists in a 100-fold dose range can be added. The whole system can be operated through fully automated protocols from a personal computer. Testing data shows accurate maintenance of temperature, CO and relative humidity at pre-set levels. Equine trachealis smooth muscle tissues tested in the system showed no signs of infection after 72 h with incubation medium replacement every 24 h. Methacholine dosing and electrical field stimulation every 4 h showed consistent responses. In conclusion, the developed system is a great improvement on the manual incubation techniques being used thus far, improving on time resolution, repeatability and robustness, while reducing contamination risk and tissue damage from repeated handling.
Topics: Animals; Horses; Carbon Dioxide; Muscle, Smooth; Muscle Contraction; Methacholine Chloride; Cells, Cultured
PubMed: 37058766
DOI: 10.1016/j.jbiomech.2023.111577 -
International Forum of Allergy &... Jan 2018Cholinergic stimulation plays a major role in inflammatory airway diseases. However, its role in airway surface liquid homeostasis and aquaporin 5 (AQP5) regulation...
BACKGROUND
Cholinergic stimulation plays a major role in inflammatory airway diseases. However, its role in airway surface liquid homeostasis and aquaporin 5 (AQP5) regulation remains unclear. In this study we sought to determine the effects of methacholine and dexamethasone on AQP5 expression in human nasal epithelial cells (HNEpC).
METHODS
HNEpC were cultured with methacholine or dexamethasone at 4 concentrations in vitro. The subcellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of methacholine and dexamethasone on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), AQP5, and nuclear factor-kappaB (NF-κB) were examined using Western blotting.
RESULTS
AQP5 was found to be located in cell membrane and cytoplasm and present in every group without a statistically significant difference. Methacholine inhibited expression of AQP5 and p-CREB in HNEpC, whereas dexamethasone increased these protein levels dose-dependently in a statistically significant manner. In turn, HNEpC treated with methacholine and dexamethasone showed the same trends as those intervened separately with these 2 drugs. Moreover, dexamethasone had the ability to reverse the inhibitory effect of methacholine. Western blotting revealed that, after incubation with 10 mol/L methacholine, NF-κB increased significantly, by 186.67%, compared with the untreated control group. Again, such an increase could be significantly reversed after dexamethasone treatment.
CONCLUSION
NF-κB activation is important for inhibition of p-CREB/AQP5 expression after methacholine intervention, and dexamethasone adjusts it to the opposite side. This observation could provide additional insight into the anti-inflammatory effects of glucocorticoids that contribute to maintaining airway surface liquid and mucosal defense.
Topics: Aquaporin 5; Cells, Cultured; Dexamethasone; Down-Regulation; Epithelial Cells; Female; Glucocorticoids; Humans; Male; Methacholine Chloride; NF-kappa B; Nasal Mucosa
PubMed: 29083535
DOI: 10.1002/alr.22035 -
Klinische Padiatrie Sep 2022Exercise-induced bronchoconstriction (EIB) occurs frequently in children and adolescents and may be a sign of insufficient asthma control. EIB is often evaluated by...
OBJECTIVE
Exercise-induced bronchoconstriction (EIB) occurs frequently in children and adolescents and may be a sign of insufficient asthma control. EIB is often evaluated by respiratory symptoms, spirometry, eNO measurement and methacholine testing (MCT) instead of time consuming exercise test. Aim of this study was to analyse the amount of patients for which an exercise challenge in a cold chamber (ECC) was needed for a clear EIB diagnosis, to characterize EIB phenotypes and the incidence of exercise induced laryngeal obstruction (EILO) in a large cohort of patients with EIB.
METHODS
A retrospective analysis was performed in 595 children and adolescents (mean age 12.1 years) with suspected EIB from January 2014 to December 2018. Complete data sets of skin prick test, spirometry, eNO and MCT were available from 336 patients.
RESULTS
An ECC to confirm the EIB diagnosis was performed in 125 (37.2%) of patients. Three EIB phenotypes were detected: group 1: EIB without allergic sensitization (n=159); group 2: EIB with other than house dust mite (HDM) sensitization (n=87) and group 3: EIB with HDM sensitization (n=90). MCT and eNO showed significant differences between the subgroups: An eNO>46 ppb and/or a MCT<0.1 mg was found in 23.9% vs. 50.6% vs. 57.8% in group 1-3, respectively. Significantly more patients suffered from EILO in group 1 compared to group 2 and 3 (n=13 vs. n=1).
CONCLUSION
EIB without sensitization is as often as EIB with sensitization. In patients without sensitization, EILO has to be considered as a possible cause of symptoms during exercise.
Topics: Asthma, Exercise-Induced; Bronchoconstriction; Humans; Methacholine Chloride; Nitric Oxide; Retrospective Studies
PubMed: 35114701
DOI: 10.1055/a-1717-2178 -
Pediatric Pulmonology Mar 2020The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with...
OBJECTIVES
The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with elevated fractional exhaled nitric oxide (FeNO), a marker of type-2 inflammation in the airways.
METHODOLOGY
A total of 959 subjects from a general population, aged 12 to 15 years, answered a standardised questionnaire and underwent FeNO measurements at a screening visit at school. Adolescents without asthma, who had elevated FeNO (FeNO > 15 ppb) (n = 19), and control subjects, with low FeNO (FeNO < 5 ppb) and without reported symptoms of asthma or allergy (n = 28), participated in a follow-up study where FeNO , airway responsiveness to methacholine (PD ), blood eosinophil counts, and serum neutrophil lipocalin (HNL) and myeloperoxidase (MPO) levels were measured. Questionnaire follow-ups were performed 4 and 16 years later.
RESULTS
Airway responsiveness (PD : 6.94 [1.87, 11.39] vs 11.42 [6.33, 59.4] µmol; P < .05) and blood eosinophil counts (0.31 [0.20, 0.44] vs 0.13 [0.1, 0.22] 10 /L; P < .001) (geometric mean [95% CI]) were higher among cases than controls. A significant correlation between blood eosinophils and FeNO was found (rho = 0.41; P = .005). In contrast, serum HNL and MPO were lower in cases than controls (P < .05 both), and there was a negative correlation between HNL and FeNO (r = -0.31; P = .04). At both follow-ups, a higher proportion of subjects reported allergic symptoms compared with baseline (P = .02, P = .01).
CONCLUSIONS
Elevated FeNO in nonasthmatic adolescents was associated with airway hyperresponsiveness, elevated blood eosinophil counts, and lower systemic activation of neutrophils.
Topics: Adolescent; Adult; Asthma; Biomarkers; Bronchial Hyperreactivity; Child; Eosinophils; Exhalation; Female; Follow-Up Studies; Humans; Leukocyte Count; Lipocalins; Male; Methacholine Chloride; Nitric Oxide; Respiratory System; Young Adult
PubMed: 31944632
DOI: 10.1002/ppul.24578 -
The Journal of Asthma : Official... Jun 2017The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical...
Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients.
OBJECTIVES
The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers.
METHODS
Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test.
RESULTS
Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04.
CONCLUSIONS
Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.
Topics: Adult; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Bronchodilator Agents; Cross-Sectional Studies; Female; Humans; Inflammation; Inflammation Mediators; Male; Mannitol; Methacholine Chloride; Middle Aged; Nitric Oxide; Respiratory Function Tests; Sensitivity and Specificity; Severity of Illness Index; Skin Tests
PubMed: 27686218
DOI: 10.1080/02770903.2016.1238926