Bronchial allergy in cystic fibrosis

Wönne, R; Hofmann, Dietrich; Posselt, Hans-Georg; Stover, Bert; Bender, S. W.

doi:10.1111/j.1365-2222.1985.tb02295.x

Cited by 13 publications

(5 citation statements)

References 21 publications

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“…Overall, 61% of patients showed a significant reaction as a result of BAP. These data are in line with a study that demonstrated that even among weak skin reactions to A fumigatus , 43% are associated with a positive reaction in BAP . Furthermore, the hypothesis that sensitization translates to clinical susceptibility like an asthmatic reaction was demonstrated by a significant correlation between sIgE sensitization (quantification) to cumulative BAP dose sensitivity.…”

Section: Discussionsupporting

confidence: 82%

“…These data are in line with a study that demonstrated that even among weak skin reactions to A fumigatus, 43% are associated with a positive reaction in BAP. 33 Furthermore, the hypothesis that sensitization translates to clinical susceptibility like an asthmatic reaction was demonstrated by a significant correlation between sIgE sensitization (quantification) to cumulative BAP dose sensitivity. In addition, eNO significantly increased after 24 hours, and patients with an LAR had significantly higher eNO levels compared to patients with a negative BAP.…”

Section: Discussionmentioning

confidence: 99%

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Clinical relevance of Aspergillus fumigatus sensitization in cystic fibrosis

Eickmeier

Zissler

Wittschorek

et al. 2020

Clin Experimental Allergy

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Rationale The clinical relevance of sensitization to Aspergillus (A) fumigatus in cystic fibrosis (CF) is unclear. Some researchers propose that specific A fumigatus IgE is an innocent bystander, whereas others describe it as the major cause of TH‐2‐driven asthma‐like disease. Objectives Lung function parameters in mild CF patients may be different in patients with and without A fumigatus sensitization. We aimed to ascertain whether allergen exposure to A fumigatus by bronchial allergen provocation (BAP) induces TH‐2 inflammation comparable to an asthma‐like disease. Methods A total of 35 patients, aged 14.8 ± 8.5 years, and 20 healthy controls were investigated prospectively. The patients were divided into two groups: group 1 (n = 18): specific (s)IgE negative, and group 2 (n = 17): sIgE positive (≥0.7 KU/L) for A fumigatus. Lung function, exhaled NO, and induced sputum were analysed. All sensitized patients with an FEV1 > 75% (n = 13) underwent BAP with A fumigatus, and cell counts, and the expression of IL‐5, IL‐13, INF‐γ, and IL‐8 as well as transcription factors T‐bet, GATA‐3, and FoxP3, were measured. Results Lung function parameters decreased significantly compared to controls, but not within the CF patient group. After BAP, 8 of 13 patients (61%) had a significant asthmatic response and increased eNO 24 hours later. In addition, marked TH‐2‐mediated inflammation involving eosinophils, IL‐5, IL‐13, and FoxP3 became apparent in induced sputum cells. Conclusion Our study demonstrated the clinical relevance of A fumigatus for the majority of sensitized CF patients. A distinct IgE/TH‐2‐dominated inflammation was found in induced sputum after A fumigatus exposure.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Clinical relevance of Aspergillus fumigatus sensitization in cystic fibrosis

Eickmeier

Zissler

Wittschorek

et al. 2020

Clin Experimental Allergy

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“…In addition to exacerbated pulmonary inflammation, CF patients manifest airway obstruction and wheezing [20] and near 40-50% of these patients have airway constriction. This led us to explore the mediators involved in the induction of airway constriction in CFTR -/- mice.…”

Section: Discussionmentioning

confidence: 99%

Cytosolic phospholipase A2α mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice

Abolhassani

Ollero

et al. 2010

Respir Res

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BackgroundLungs of cystic fibrosis (CF) patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated. Aim: to examine the effect of P. aeruginosa LPS on airway constriction in CF mice and the implication in this process of cytosolic phospholipase A2α (cPLA2α), an enzyme involved in arachidonic acid (AA) release.MethodsMice were instilled intra-nasally with LPS. Airway constriction was assessed using barometric plethysmograph. MIP-2, prostaglandin E2 (PGE2), leukotrienes and AA concentrations were measured in BALF using standard kits and gas chromatography.ResultsLPS induced enhanced airway constriction and AA release in BALF of CF compared to littermate mice. This was accompanied by increased levels of PGE2, but not those of leukotrienes. However, airway neutrophil influx and MIP-2 production remained similar in both mouse strains. The cPLA2α inhibitor arachidonyl trifluoro-methyl-ketone (ATK), but not aspirin which inhibit PGE2 synthesis, reduced LPS-induced airway constriction. LPS induced lower airway constriction and PGE2 production in cPLA2α -/- mice compared to corresponding littermates. Neither aspirin nor ATK interfered with LPS-induced airway neutrophil influx or MIP-2 production.ConclusionsCF mice develop enhanced airway constriction through a cPLA2α-dependent mechanism. Airway inflammation is dissociated from airway constriction in this model. cPLA2α may represent a suitable target for therapeutic intervention in CF. Attenuation of airway constriction by cPLA2α inhibitors may help to ameliorate the clinical status of CF patients.

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“…All other aminoglycosides, but not the commercially available form of amikacin in France (Amiklin1), contain sulphites that may be responsible for severe allergic side effects [14]. This is particularly important in CF patients who are known to have frequent bronchial hyperreactivity [15] and are at risk of bronchial allergy [16], and this is why the present study was conducted with amikacin. In the present study, tolerance of inhalation was good for all patients and pulmonary function tests were unchanged after nebulization.…”

Section: Discussionmentioning

confidence: 99%

Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis

et al. 2001

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Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized byPseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL.Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polorization immunoassay (FPIA).The mean±sem MDL was 14.0±2.2% of the nebulizer charge. The mean±sem amount of amikacin excreted in the urine was 20.9±4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine.Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.

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Bronchial allergy in cystic fibrosis

Cited by 13 publications

References 21 publications

Clinical relevance of Aspergillus fumigatus sensitization in cystic fibrosis

Clinical relevance of Aspergillus fumigatus sensitization in cystic fibrosis

Cytosolic phospholipase A2α mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice

Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis

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