Andrei Malinovschi

Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects.

BACKGROUND Fraction of exhaled nitric oxide (Feno) and blood eosinophil count (B-Eos) values, markers of local and systemic eosinophilic inflammation, respectively, are increased in asthmatic patients. Little is known about the relation of these markers to reported wheeze and asthma events in a random population sample. OBJECTIVES We sought to determine the individual and independent values of B-Eos and Feno in relation to wheeze, asthma diagnosis, and asthma events in a cross-sectional study. METHODS Feno and B-Eos values were measured in 12,408 subjects aged 6 to 80 years from the National Health and Nutrition Examination Survey 2007-2008 and 2009-2010. Current wheeze and asthma diagnosis, as well as asthma attacks and asthma-related emergency department (ED) visits within the last 12 months, were assessed by means of questionnaires. RESULTS Intermediate or high Feno values and intermediate or high B-Eos values were independently associated with having asthma, wheeze, and asthma attacks. However, only intermediate and high B-Eos values were independently associated with asthma-related ED visits. High Feno (≥ 50 ppb) and B-Eos (≥ 500 cells/mm(3)) values rendered an adjusted odds ratio of 4.5 of having wheeze, 5.1 of having asthma, 5.4 for asthma attacks, and 2.9 for asthma-related ED visits compared with normal Feno (<25 ppb) and B-Eos (<300 cells/mm(3)) values. CONCLUSIONS Exhaled nitric oxide and B-Eos values offered independent information in relation to the prevalence of wheeze, asthma diagnosis, and asthma events in this random population sample. The clinical importance of these findings in asthmatic patients with regard to phenotyping and individualized treatment, considering both local and systemic eosinophilic inflammation, needs to be determined.

Population-based study of multiplexed IgE sensitization in relation to asthma, exhaled nitric oxide, and bronchial responsiveness

BACKGROUND IgE sensitization is an important risk factor for the development of asthma. OBJECTIVE The aim of this study was to investigate the IgE antibody profile for a broad spectrum of allergen molecules in asthmatic patients. METHODS Participants from the European Community Respiratory Health Survey II (n=467) were tested with ImmunoCAP ISAC against 103 allergen molecules. The presence of bronchial hyperresponsiveness was measured with a methacholine challenge test and bronchial inflammation with fraction of exhaled nitric oxide (Feno). RESULTS A total of 38% of the controls and 72% of the asthmatic patients were sensitized against at least 1 of the allergen components (P<.0001). Asthma was independently related to having IgE antibodies against pollen (odds ratio=2.2) and perennial airway allergens (odds ratio=5.6), increased Feno was independently related to having IgE antibodies against food allergens and perennial allergens, while bronchial responsiveness was independently associated with having IgE antibodies against only perennial allergens. Sensitization to food allergens was related to asthma and increased Feno if IgE antibody against pollen allergens was present. Simultaneous sensitization to perennial, pollen, and food allergens involves the highest risk of asthma (odds ratio=18.3), bronchial inflammation, and responsiveness. CONCLUSIONS Feno, bronchial responsiveness, and the risk of asthma increase with multiple sensitizations to different allergen groups. We show for the first time that the presence of IgE antibodies against food allergens is independently associated with increased Feno and increases the risk of asthma in subjects with simultaneous sensitization to pollen allergens.

IgE sensitisation in relation to flow-independent nitric oxide exchange parameters

BackgroundA positive association between IgE sensitisation and exhaled NO levels has been found in several studies, but there are no reports on the compartment of the lung that is responsible for the increase in exhaled NO levels seen in IgE-sensitised subjects.MethodsThe present study comprised 288 adult subjects from the European Community Respiratory Health Survey II who were investigated in terms of lung function, IgE sensitisation (sum of specific IgE), smoking history and presence of rhinitis and asthma. Mean airway tissue concentration of NO (CawNO), airway transfer factor for NO (DawNO), mean alveolar concentration of NO (CalvNO) and fractional exhaled concentration of NO at a flow rate of 50 mL s-1 (FENO 0.05) were determined using the extended NO analysis.ResultsIgE-sensitised subjects had higher levels (geometric mean) of FENO 0.05 (24.9 vs. 17.3 ppb) (p < 0.001), DawNO (10.5 vs. 8 mL s-1) (p = 0.02) and CawNO (124 vs. 107 ppb) (p < 0.001) and positive correlations were found between the sum of specific IgE and FENO 0.05, CawNO and DawNO levels (p < 0.001 for all correlations). Sensitisation to cat allergen was the major determinant of exhaled NO when adjusting for type of sensitisation. Rhinitis and asthma were not associated with the increase in exhaled NO variables after adjusting for the degree of IgE sensitisation.ConclusionThe presence of IgE sensitisation and the degree of allergic sensitisation were related to the increase in airway NO transfer factor and the increase in NO concentration in the airway wall. Sensitisation to cat allergen was related to the highest increases in exhaled NO parameters. Our data suggest that exhaled NO is more a specific marker of allergic inflammation than a marker of asthma or rhinitis.

Anti-inflammatory Treatment of Atopic Asthma Guided by Exhaled Nitric Oxide: A Randomized, Controlled Trial

BACKGROUND Atopic asthma is characterized by Th2 cytokine-driven inflammation of the airway mucosa, which is signaled by the fraction of exhaled nitric oxide (FENO). OBJECTIVE We tested whether an FENO-guided anti-inflammatory treatment algorithm could improve asthma-related quality of life and asthma symptom control, and reduce exacerbations in atopic asthmatics within primary care. METHODS Altogether, 187 patients with asthma and who were nonsmokers (age range, 18-64 years) with perennial allergy and who were on regular inhaled corticosteroid treatment were recruited at 17 primary health care centers, randomly assigned to 2 groups and followed up for 1 year. For the controls (n = 88), FENO measurement was blinded to both operator and patient, and anti-inflammatory treatment was adjusted according to usual care. In the active group (n = 93), treatment was adjusted according to FENO. Questionnaires on asthma-related quality of life (Mini Asthma Quality of Life Questionnaire) and asthma control (Asthma Control Questionnaire) were completed, and asthma events were noted. RESULTS The Asthma Control Questionnaire score change over 1 year improved significantly more in the FENO-guided group (-0.17 [interquartile range {IQR}, -0.67 to 0.17] vs 0 [-0.33 to 0.50]; P = .045), whereas the Mini Asthma Quality of Life Questionnaire score did not (0.23 [IQR, 0.07-0.73] vs 0.07 [IQR, -0.20 to 0.80]; P = .197). The change in Asthma Control Questionnaire was clinically important in subpopulations with poor control at baseline (P = .03). Furthermore, the exacerbation rate (exacerbations/patient/y) was reduced by almost 50% in the FENO-guided group (0.22 [CI, 0.14-0.34] vs 0.41 [CI, 0.29-0.58]; P = .024). Mean overall inhaled corticosteroid use was similar in both groups (P = .95). CONCLUSION Use of FENO to guide anti-inflammatory treatment within primary care significantly reduced the exacerbation rate and improved asthma symptom control without increasing overall inhaled corticosteroid use.

Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey.

Asthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality‐of‐life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects.

Oxidative stress and airway inflammation after allergen challenge evaluated by exhaled breath condensate analysis.

Background Allergen exposure may increase airway oxidative stress, which causes lipid membrane peroxidation and an increased formation of 8‐isoprostane.

Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma

We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population‐based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization.

Clinical aspects of using exhaled NO in asthma diagnosis and management

Current guidelines recommend tailoring of asthma management according to disease control, which is largely defined by increased symptoms and deterioration in lung function. These features do not reflect the severity nor the type of the asthmatic airway inflammation. Fractional exhaled nitric oxide (FENO) is a simple, non‐invasive and cost‐effective online test applicable in both adults and children. In addition to symptoms and lung function measurements, FENO reflects airway eosinophilia and hence allows online assessment of the corticosteroid‐sensitive T helper 2 type airway inflammation in asthmatic patients. FENO can thus be applied to aid asthma diagnosis and treatment monitoring both in clinical practice and for research purposes.

Ten-year review reveals changing trends and severity of allergic reactions to nuts and other foods.

Over the past few decades, the incidence of food allergies has risen and Sweden has increased its import of peanuts and exotic nuts, such as cashew nuts, which may cause severe allergic reactions. This study aimed to retrospectively investigate paediatric emergency visits due to food reactions over a 10‐year period, focusing on reactions to peanuts and tree nuts.

The value of exhaled nitric oxide to identify asthma in smoking patients with asthma-like symptoms

BACKGROUND The fraction of nitric oxide in exhaled air (FeNO) is used in asthma diagnosis and management. Smoking reduces FeNO and 20-35% of asthmatics are smoking. However no guidelines exist on the diagnostic value of FeNO in smokers. Therefore we assessed the value of FeNO to diagnose asthma in a population of subjects with asthma-like symptoms and different smoking habits. METHODS Measurements of FeNO, lung function, bronchial responsiveness and allergy testing were performed in 282 subjects (108 never-, 62 ex- and 112 current smokers) aged 14-44 years, with symptoms suggestive of asthma. These subjects were a subset of subjects reporting respiratory symptoms (n = 686) in a random population sample (n = 10,400). RESULTS A diagnosis of asthma was given to 96 of the 282 subjects. Subjects with asthma had higher FeNO levels than subjects with non-specific asthma symptoms in all three smoking strata (p < 0.001), with a percentual increase of FeNO by 76% in never-, 71% in ex- and 60% in current smokers. The area under the ROC-curve was similar in never-, ex- and current smokers (0.72 vs. 0.74 vs. 0.70). The cut-offs were approximately 30% lower for either 90% specificity (22 vs. 31 ppb) or 90% sensitivity (7 vs. 10 ppb) in current vs. never-smokers. CONCLUSIONS FeNO could differentiate asthmatic subjects from non-asthmatic subjects with asthma-like symptoms equally well in both never- and current smokers within a random population sample. The FeNO cut-off levels needed in order to achieve high sensitivity or specificity were lower in current smokers.