Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

Yoo, Yung Joon; Yu, Jinho; Kim, D. K.; Choi, Sun Hee; Kim, C. K.; Koh, Young Yull

doi:10.1183/09031936.06.00019605

Cited by 18 publications

(14 citation statements)

References 29 publications

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“…This study was a retrospective analysis of the database of asthmatic children who have been challenged with methacholine and AMP from November 2005 through December 2006 for inclusion in our clinical studies (12, 13).…”

Section: Methodsmentioning

confidence: 99%

Methacholine and adenosine 5′‐monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma

Suh

Lee

Kim

et al. 2011

Pediatric Allergy Immunology

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The relationship between atopy and bronchial hyperresponsiveness (BHR), both key features of asthma, remains to be clarified. BHR is commonly evaluated by bronchial challenges using direct and indirect stimuli. The aim of this study was to investigate the degree of BHR to methacholine (direct stimulus) and adenosine 5'-monophosphate (AMP) (indirect stimulus) according to the presence and degree of atopy in children with asthma. We performed a retrospective analysis of data from 120 children presenting with a diagnosis of asthma. These children were characterized by skin-prick tests (SPTs), spirometry and bronchial challenges with methacholine and AMP. Atopy was defined by at least one positive reaction to SPTs, and its degree was measured using serum total IgE levels, number of positive SPTs and atopic scores (sum of graded wheal size). A provocative concentration causing a 20% decline in FEV(1) (PC(20) ) was determined for each challenge. Patients with atopy(n=94) had a significantly lower AMP PC(20) than non-atopic patients (n=26), whereas methacholine PC(20) was not different between the two groups. Among the patients with atopy, there was no association between methacholine PC(20) and any atopy parameter. In contrast, a significant association was found between AMP PC(20) and the degree of atopy reflected in serum total IgE, number of positive SPTs and atopic scores (anova trend test, p=0.002, 0.001, 0.003, respectively). AMP responsiveness was associated with the presence and degree of atopy, whereas such a relationship was not observed for methacholine responsiveness. These findings suggest that atopic status may be better reflected by bronchial responsiveness assessed by AMP than by methacholine.

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Section: Methodsmentioning

confidence: 99%

Methacholine and adenosine 5′‐monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma

Suh

Lee

Kim

et al. 2011

Pediatric Allergy Immunology

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“…A maior parte dos pacientes com BOPI apresenta hiper-reatividade à metacolina, mas não à adenosina 5-monofosfato, enquanto que os pacientes asmáticos habitualmente respondem às duas substâncias 55 .…”

Section: Respostaunclassified

Post-infectious bronchiolitis obliterans in children

Champs

Lasmar²,

Camargos³

et al. 2011

J Pediatr (Rio J)

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Objective: To review publications about the main features of postinfectious bronchiolitis obliterans and its history, etiology, epidemiology, risk factors, pathogenesis, histological findings, clinical presentation, complementary tests, diagnostic criteria, differential diagnosis, treatment and prognosis.Sources: Non-systematic review of MEDLINE and LILACS databases and selection of 66 most relevant studies. Summary of the findings:In the post-infectious bronchiolitis obliterans there is an insult to respiratory epithelial cells, and its clinical severity is associated with the degree of lesion and inflammation. Diagnosis is made according to clinical signs and symptoms, by exclusion of main differential diagnoses and with the aid of complementary tests. High resolution CT, particularly images obtained during inspiration and expiration, provide information for the evaluation of the small airways. Pulmonary function tests show fixed airway obstructions and marked decrease of FEF 25-75% . Treatment has not been definitely established, and corticoids have been administered as pulse therapy or by inhalation of high doses of steroids. However, data about its efficacy are scarce in the literature. Long-term prognosis is variable, and there might be either clinical improvement or deterioration into respiratory insufficiency and death.Conclusion: Post-infectious bronchiolitis obliterans is a disease with a high morbidity rate; it should be treated by a multidisciplinary team, and patients should be followed up for a long period of time.J Pediatr (Rio J). 2011;87(3):187-198: Bronchiolitis obliterans, diagnosis, spirometry, CT, child. ResumoObjetivo: Revisar os trabalhos publicados sobre os principais aspectos da bronquiolite obliterante pós-infecciosa, relacionados com sua história, etiologia, epidemiologia, fatores de risco, patogenia, alterações histológicas, manifestações clínicas, exames complementares, critérios diagnósticos, diagnóstico diferencial, tratamento e prognóstico. Fonte dos dados:Realizou-se uma revisão não sistemática nas bases de dados MEDLINE e LILACS, selecionando-se 66 referências mais relevantes. Síntese dos dados:Na bronquiolite obliterante pós-infecciosa ocorre lesão do epitélio respiratório, e a gravidade clínica está relacionada aos diferentes graus de lesão e ao processo inflamatório. O diagnóstico baseia-se no quadro clínico, na exclusão dos principais diagnósticos diferenciais e no auxílio dos exames complementares. A tomografia computadorizada de alta resolução, principalmente com imagens em inspiração e expiração, possibilta a avaliação das pequenas vias aéreas. As provas de função pulmonar caracterizam-se por padrão obstrutivo fixo com redução acentuada do FEF 25-75% . O tratamento não está bem estabelecido, e o uso de corticoides tem sido preconizado em forma de pulsoterapia ou por via inalatória em elevadas doses, no entanto, os dados da literatura a respeito de sua eficácia ainda são escassos. O prognóstico a longo prazo é variável, podendo haver melhora clínica ou evolução par...

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“…53 Also, doses ranging from 0.075 to 50 mg/ml were used to measure AHR in children with post-infectious bronchiolitis obliterans. 54 Regarding the increases in levels of cytokines (IL-4, IL-5, TNF-a), OVA-specific IgE, and total and differential white cells in BALF, all treatments (except formoterol) significantly reversed these OVA-induced changes mainly with the roflumilast þ fluticasone group. The combinations showed significant variations from monotherapies and the effects of the roflumilast þ fluticasone combination were the most significant.…”

Section: Discussionmentioning

confidence: 89%

Co-inhalation of roflumilast, rather than formoterol, with fluticasone more effectively improves asthma in asthmatic mice

Murad

Habıb

Rafeeq

et al. 2017

Exp Biol Med (Maywood)

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Impact statementRoflumilast, a selective phosphodiesterase-4 inhibitor, was approved for the treatment of chronic obstructive pulmonary disease (COPD). This study showed that co-inhalation of roflumilast and fluticasone significantly decreased airway hyperresponsiveness in ovalumin-asthmatic mice. Also, it more significantly improved inflammation and histopathological changes than co-inhalation of formoterol and fluticasone. The current results showed that inhaled roflumilast reduced counts of eosinophils, neutrophils, and macrophages in bronchoalveolar lavage fluid. Consequently, inhaled roflumilast might be of potential off-label benefit in treatment of eosinophilic and neutrophilic asthma and asthma-COPD overlap syndrome (ACOS). These results could also support other experimental and clinical studies addressing the same issue. AbstractRoflumilast is approved as an add-on therapy for chronic obstructive pulmonary disease. The inflammation in chronic obstructive pulmonary disease is mainly neutrophilic, while in asthma it is mainly eosinophilic, studies addressing role of roflumilast in eosinophilic inflammation are recommended. Also in severe asthma, the dominant inflammatory cells are neutrophils. Thus, roflumilast has a potential off-label use in the treatment of asthma. This study was designed to evaluate the effects of co-inhalation of roflumilast and fluticasone compared to that of formoterol and fluticasone in ovalbumin-sensitized and-challenged BALB/c mice. Besides normal control group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n ¼ 8): positive control, vehicle-treated, and five drug-treated groups. Treatments (mg/kg) were given as 15 min-inhalation once/day for five days as follows: roflumilast (500), formoterol (50), fluticasone (1000), roflumilast þ fluticasone (500 þ 1000), and formoterol þ fluticasone (50 þ 1000). Penh values were measured in conscious unrestrained mice using the single-chamber whole-body plethysmography. Airway hyperreactivity to inhaled methacholine was evaluated. Bronchoalveolar lavage fluid was used for the measurements of levels of IL-4, IL-5, TNF-a, OVA-specific IgE, and total and differential white cells. Lung sections were stained with hematoxylin and eosin and periodic acid-Schiff. The asthmatic mice showed significant increases in airway hyperreactivity which were significantly reversed by the combination treatments. The asthmatic mice showed significant increases in levels of IL-4, IL-5, TNF-a, ovalbumin-specific IgE, and total and differential white cells in bronchoalveolar lavage fluid. All treatments (except formoterol) significantly reversed these changes mainly with roflumilast þ fluticasone. The asthmatic mice showed severe inflammatory infiltration and goblet cell hyperplasia which were maximally reversed by roflumilast þ fluticasone, while minimally reversed by formoterol. In conclusion, co-inhalation of roflumilast þ fluticasone more significantly improved inflammation and histopathological changes than co-inhalation of formoterol þ f...

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Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans

Cited by 18 publications

References 29 publications

Methacholine and adenosine 5′‐monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma

Methacholine and adenosine 5′‐monophosphate (AMP) responsiveness, and the presence and degree of atopy in children with asthma

Post-infectious bronchiolitis obliterans in children

Co-inhalation of roflumilast, rather than formoterol, with fluticasone more effectively improves asthma in asthmatic mice

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