Methacholine challenge does not affect bronchoalveolar fluid cell number and many indices of cell function in asthma

Kraft, Monica; Bettinger, C. M.; Wenzel, Sally E.; Irvin, Charles G.; Ackerman, S.J.; Martin, Richard J.

doi:10.1183/09031936.95.08111966

Cited by 18 publications

(13 citation statements)

References 22 publications

(28 reference statements)

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“…BAL fluid return was similar in subjects with asthma and control subjects and percent BAL eosinophils present were greater in subjects with asthma, as expected (22). There were no significant differences in total cell count observed (not shown).…”

Section: Bal Cell Count and Differentialsupporting

confidence: 60%

“…However, the concentrations of LMW SNOs measured in this study were quite low (z10 nM) compared with reduced glutathione (GSH) and would not be expected to significantly contribute to the increased GSSG levels (z300 nM) previously reported to be present in the lavage fluid in asthma (25). BAL SNO levels have been shown to be diminished in subjects with mild and severe asthma at baseline (4,22). Previously two soluble protein fractions from guinea pig lung homogenate have been identified, which break down SNO and prevent airway smooth muscle relaxation in vitro (26).…”

Section: Discussionmentioning

confidence: 93%

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S-Nitrosoglutathione Reductase

Que

Yang

Stamler

et al. 2009

Am J Respir Crit Care Med

102

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Rationale: Nitric oxide bioactivity, mediated through the formation of S-nitrosothiols (SNOs), has a significant effect on bronchomotor tone. S-Nitrosoglutathione is an endogenous bronchodilator that is decreased in children with asthmatic respiratory failure and in adults with asthma undergoing segmental airway challenge. Recently we showed that S-nitrosoglutathione reductase (GSNOR) regulates endogenous SNOs. Mice with genetic deletion of GSNOR are protected from airway hyperresponsivity in an allergic asthma model. Objectives: We hypothesized that GSNOR is increased in human asthma and correlates with lung SNO content and airway reactivity. Methods: We recruited 36 subjects with mild asthma with FEV 1 88.5 6 2.3% predicted and 34 healthy control subjects with FEV 1 100.7 6 2.5% predicted. Bronchoalveolar lavage (BAL) was performed in all subjects. Cell counts, differentials, GSNOR activity, and SNO levels were determined in BAL. Measurements and Main Results: SNO content was decreased in asthmatic BAL compared with control BAL and correlated inversely with GSNOR expression in BAL cell lysates. Furthermore, GSNOR activity measured from BAL samples was significantly increased in subjects with asthma compared with control subjects and correlated inversely with the provocative concentration of methacholine causing a 20% decrease in FEV 1 . Conclusions: These findings suggest that GSNOR is an important regulator of airway SNO content and airways hyperresponsiveness in human asthma.

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Section: Bal Cell Count and Differentialsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 93%

S-Nitrosoglutathione Reductase

Que

Yang

Stamler

et al. 2009

Am J Respir Crit Care Med

102

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“…Subjects underwent bronchoscopy with endobronchial biopsy as previously described [12]. The site of biopsy was randomised to either the right or left lower lobe and five-to-six endobronchial biopsy specimens were taken from the tertiary carinae of the right or left lower lobes, under direct visualisation.…”

Section: Bronchoscopymentioning

confidence: 99%

“…Fibroblasts were cultured from endobronchial biopsy tissue as previously described [12]. Briefly, biopsy specimens were rinsed and cut into several small pieces (,five-six per biopsy) and placed into wells (two pieces?well -1 ) of a 24-well tissue culture plate, containing DMEM, supplemented with 10% FBS, streptomycin (100 mg?mL -1 ), penicillin (10,000 U?mL -1 ), and gentamicin (100 mg?mL -1 ).…”

Section: Fibroblast Culturementioning

confidence: 99%

Dexamethasone can stimulate G1-S phase transition in human airway fibroblasts in asthma

Fouty

Moss

Solodushko

et al. 2006

European Respiratory Journal

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Corticosteroids are the first line of therapy for asthma. Whether they alter the progression of airway remodelling in asthma is, as yet, unknown.To determine whether corticosteroids could alter the fibroblast cell cycle the current authors studied the effect of dexamethasone on cultured airway fibroblasts obtained from nine mild-tomoderate, steroid-naïve asthmatics (forced expiratory volume in one second 78¡4% predicted), and seven normal controls. Fibroblasts were cultured from endobronchial biopsies obtained via bronchoscopy. Cells were exposed to dexamethasone (10 -9 -10 -7 M) and studied at 72 h to determine differences in progression through the cell cycle.In asthmatic fibroblasts, dexamethasone, at concentrations of 10 -8M and 10 -7 M, nearly doubled the number of cells in the S phase (17.8¡3.0% and 18.4¡3.1%, respectively) compared with untreated fibroblasts (10.3¡1.4%). There was no significant effect in normal control fibroblasts. Dexamethasone induced hyperphosphorylation of the tumour suppressor, retinoblastoma (RB) in asthmatic fibroblasts; fibroblasts from normal controls had significantly less hyperphosphorylation of RB. No difference in protein expression of the CCAAT/enhancer binding protein a between the two groups was detected. This study suggests that dexamethasone can stimulate G1-S phase cell cycle transition in human airway fibroblasts obtained from asthmatics. Whether this leads to enhanced airway remodelling in some individuals remains to be determined.

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“…Além do que, as medidas com histamina são menos reprodutí-veis (1) . Além da conhecida ação da metacolina no múscu-lo liso brônquico, foram identificados receptores muscarí-nicos para a acetilcolina (e, portanto, para metacolina) em células endoteliais, epiteliais, neutrófilos, linfócitos, mastócitos, monócitos e macrófagos (10) , o que poderia sugerir um papel pró-inflamatório da metacolina empregada na broncoprovocação. Porém, esse papel não se confirmou neste estudo e nem em trabalhos prévios.…”

Section: Discussionunclassified

Avaliação da inflamação de vias aéreas em asmáticos após o teste de broncoprovocação com metacolina

et al. 2001

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Introdução: O teste de broncoprovocação com metacolina é comumente empregado em pneumologia para medir a reatividade brônquica com finalidade de diagnóstico ou acompanhamento da asma. Objetivo: Pesquisar efeitos tardios da inalação de metacolina na inflamação brônquica avaliada pelo escarro induzido. Casuística e métodos: Foram selecionados dez pacientes com asma leve ou moderada, não tabagistas, com medicação e quadro clínico estáveis. Às 12:00h, os pacientes receberam inalação, aleatoriamente designada, de metacolina (broncoprovocação) ou soro fisiológico. Às 18:00h, foi realizada a indução de escarro. Em outro dia, com intervalo de uma semana, os pacientes completaram o protocolo, recebendo a outra inalação (metacolina ou soro fisiológico) e nova indução de escarro. Resultados: Após metacolina, obtiveram-se 8,6 ± 9g de escarro, 8,6 ± 6 milhões de células, sendo 78 ± 10% viáveis e 6,8 ± 7% eosinófilos. Esses dados não foram significativamente diferentes dos resultados obtidos após soro fisiológico: escarro = 7,6 ± 6g, células = 12,4 ± 12 milhões, 82 ± 10% viáveis e 6,6 ± 9% eosinófilos. A queda de pico de fluxo observada durante a indução de escarro também não diferiu: 21,4 ± 12% após metacolina e 18,4 ± 15% após soro fisiológico. A queda de pico de fluxo durante a indução correlacionou-se com a quantidade de escarro (p = 0,018) e percentagem de eosinófilos (p = 0,003). Outras correlações entre parâmetros funcionais e do escarro não foram significantes. Conclusão: O teste de broncoprovocação com metacolina realizado seis horas antes da indução de escarro não altera significativamente a quantidade e nem a constituição celular do escarro.

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Methacholine challenge does not affect bronchoalveolar fluid cell number and many indices of cell function in asthma

Cited by 18 publications

References 22 publications

S-Nitrosoglutathione Reductase

S-Nitrosoglutathione Reductase

Dexamethasone can stimulate G1-S phase transition in human airway fibroblasts in asthma

Avaliação da inflamação de vias aéreas em asmáticos após o teste de broncoprovocação com metacolina

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