Bronchial inflammation in hypersensitivity pneumonitis after antigen‐specific inhalation challenge

Villar, Ana; Muñoz, Xavier; Sánchez-Vidaurre, Sara; Gómez-Ollés, Susana; Morell, Ferrán; Cruz, María Jesús

doi:10.1111/resp.12323

Cited by 19 publications

(9 citation statements)

References 36 publications

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“…A study on farmer's lung, another type of HP, revealed that large numbers of lymphocytes and high levels of IL-2 are present in the bronchoalveolar lavage fluid of people exposed to allergens, which might result in lymphocyte accumulation in the lung. Moreover, serum soluble IL-2 receptor was found to be expressed at a high level [17], and PF and Th2 dominance were observed when the disease evolved to the chronic stage; IL-4 was also produced by Th2 cells at a higher level [8]. In our previous study, Th1-associated cytokines were found to be highly expressed in PBL patients.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Associations of Pulmonary Fibrosis with Peripheral Blood Th1/Th2 Cell Imbalance and EBF3 Gene Methylation in Uygur Pigeon Breeder’s Lung Patients

Wu¹,

Luo²,

Pang³

et al. 2018

Cell Physiol Biochem

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Background/Aims Pigeon breeder’s lung (PBL) results from Th1/Th2 cell imbalance. B cells inhibit the immune activity of Th1, and EBF3 is a key B cell factor. This study explored the relationship between EBF3 and Th1/Th2 imbalance in chronic PBL cases complicated with pulmonary fibrosis (PF). Methods Twenty Uygur PBL+PF patients, 20 pigeon breeders without PBL or PF, and 20 healthy individuals without pigeon breeding history constituted the patient I, negative control, and normal control groups, respectively. Peripheral blood specimens and case backgrounds were collected between June 2016 and March 2017. EBF3 gene methylation was analyzed by matrix assisted laser desorption ionization-time of flight mass spectrometry. To compare different mechanisms of PF progression in PBL, samples from 20 Uygur PBL patients without PF (at acute and sub-acute stages) were collected between October 2017 and February 2018, constituting the patient II group. EBF3 mRNA expression was evaluated by real-time polymerase chain reaction. IFN-γ, IL-4 and IL-10 expression and Th1/Th2 imbalance in PBL were evaluated by enzyme-linked immunosorbent assay and flow cytometry. Results CpG-2 and general methylation rates in the patient I group were lower than those in the control groups (P˂0.017). The level of EBF3 mRNA expression in the patient I group was significantly higher than that in any other group. Compared with the control groups, the patient I group showed a significantly higher level of IL-4, whereas the patient II group showed a significantly lower level. IL-10 was also expressed more highly in the patient I group than in any other group (P< 0.01). Flow cytometry showed INF-γ dominance (Th1 cytokine) in PBL at the acute/sub-acute stage and IL-4 dominance (Th2 cytokine) at the chronic stage after PF occurred. The general methylation rate was negatively correlated with the mRNA level, with the latter being positively correlated with the IL-10 level and number of pigeons bred in the past 3 months. IL-4 expression was negatively correlated with INF-γ but positively correlated with PF area and duration of pigeon breeding history. Conclusions After PF occurs in chronic PBL, the inflammation type changes from Th1 dominance to Th2 dominance. During PBL development, IL-10 increases before IL-4 does, which may be associated with EBF3 hypomethylation and the involvement of B lymphocytes.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Associations of Pulmonary Fibrosis with Peripheral Blood Th1/Th2 Cell Imbalance and EBF3 Gene Methylation in Uygur Pigeon Breeder’s Lung Patients

Wu¹,

Luo²,

Pang³

et al. 2018

Cell Physiol Biochem

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“…Although the presence of lymphocytic inflammation in the alveoli is characteristic in HP, in the bronchi it has been shown that there may be neutrophilic inflammation, especially in cases in which molds are the causative agent [ 12 , 14 ]. Our group has also recently confirmed that individuals with HP present significantly increased levels of neutrophils in induced sputum following the challenge with fungal agents [ 14 ]; this may explain the decrease in pH found in the present study after the challenge test in patients with HP caused by molds. Taken together, these findings also allow us to hypothesize that the mechanism of action of the HP may differ depending on the causative agent.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies using induced sputum have reported an increase in the total cell count and the lymphocyte count in patients with HP compared to the healthy population [ 11 – 13 ]. Also using induced sputum, our group recently demonstrated that bronchial inflammation is present in patients with HP, and is mainly evidenced by increases in neutrophils that worsen following exposure to the offending antigen during SIC [ 14 ]. However, other non-invasive methods for studying pulmonary inflammation have not been analyzed to date in patients with this disease.…”

Section: Introductionmentioning

confidence: 99%

Changes in PH in exhaled breath condensate after specific bronchial challenge test in patients with chronic hypersensitivity pneumonitis: a prospective study

et al. 2015

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BackgroundThe aim of this study was to investigate the influence of the specific inhalation challenge (SIC) on changes of pH values in exhaled breath condensate (EBC) in patients with hypersensitivity pneumonitis (HP).MethodsA prospective study of 85 patients with suspected HP, of whom 63 were diagnosed with HP due to exposure to avian or fungal antigens. In all cases, EBC samples were collected before and after completion of the SIC and pH values were determined.ResultsTaken as a whole, patients with HP did not present changes in EBC pH after SIC. However, considering only patients with exposure to molds, those diagnosed with HP had a significantly more acid pH post-SIC than those with another diagnosis (p = 0.011). This fact is not observed in patients exposed to bird’s antigens. A ROC curve showed that a reduction in EBC pH of 0.3 units or more after SIC in patients diagnosed with HP due to exposure to molds had a sensitivity of 30 % (CI: 12.8 to 54.3 %) and a specificity of 100 % (CI: 65.5 to 100 %).ConclusionEBC pH may be useful in interpreting SIC results in patients with HP, especially in those patients exposed to molds. Further studies are now required to test the validity of these proposals.

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“…In hypersensitivity pneumonitis, Villar et al . established that specific allergen challenge leads to measurable changes in inflammatory cells and protein markers in induced sputum . Overall, these studies point at the potential for utilizing novel serum and lung specific measures of disease activity to provide better understanding of disease behaviour and improved targeting of therapy.…”

Section: Rare Lung Diseasementioning

confidence: 95%

Year in review 2014: Interstitial lung disease, physiology, sleep and ventilation, acute respiratory distress syndrome, cystic fibrosis, bronchiectasis and rare lung disease

et al. 2015

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Bronchial inflammation in hypersensitivity pneumonitis after antigen‐specific inhalation challenge

Abstract: This study shows that bronchial inflammation is present in patients with HP evidenced by increases in sputum neutrophils and eosinophils following exposure to the offending antigen during SIC.

Cited by 19 publications

References 36 publications

Associations of Pulmonary Fibrosis with Peripheral Blood Th1/Th2 Cell Imbalance and EBF3 Gene Methylation in Uygur Pigeon Breeder’s Lung Patients

Associations of Pulmonary Fibrosis with Peripheral Blood Th1/Th2 Cell Imbalance and EBF3 Gene Methylation in Uygur Pigeon Breeder’s Lung Patients

Changes in PH in exhaled breath condensate after specific bronchial challenge test in patients with chronic hypersensitivity pneumonitis: a prospective study

Year in review 2014: Interstitial lung disease, physiology, sleep and ventilation, acute respiratory distress syndrome, cystic fibrosis, bronchiectasis and rare lung disease

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