Lennart Nordvall

Performance of a new hand-held device for exhaled nitric oxide measurement in adults and children.

BackgroundExhaled nitric oxide (NO) measurement has been shown to be a valuable tool in the management of patients with asthma. Up to now, most measurements have been done with stationary, chemiluminescence-based NO analysers, which are not suitable for the primary health care setting. A hand-held NO analyser which simplifies the measurement would be of value both in specialized and primary health care. In this study, the performance of a new electrochemical hand-held device for exhaled NO measurements (NIOX MINO) was compared with a standard stationary chemiluminescence unit (NIOX).MethodsA total of 71 subjects (6–60 years; 36 males), both healthy controls and atopic patients with and without asthma were included. The mean of three approved exhalations (50 ml/s) in each device, and the first approved measurement in the hand-held device, were compared with regard to NO readings (Bland-Altman plots), measurement feasibility (success rate with 6 attempts) and repeatability (intrasubject SD).ResultsSuccess rate was high (≥ 84%) in both devices for both adults and children. The subjects represented a FENO range of 8–147 parts per billion (ppb). When comparing the mean of three measurements (n = 61), the median of the intrasubject difference in exhaled NO for the two devices was -1.2 ppb; thus generally the hand-held device gave slightly higher readings. The Bland-Altman plot shows that the 95% limits of agreement were -9.8 and 8.0 ppb. The intrasubject median difference between the NIOX and the first approved measurement in the NIOX MINO was -2.0 ppb, and limits of agreement were -13.2 and 10.2 ppb. The median repeatability for NIOX and NIOX MINO were 1.1 and 1.2 ppb, respectively.ConclusionThe hand-held device (NIOX MINO) and the stationary system (NIOX) are in clinically acceptable agreement both when the mean of three measurements and the first approved measurement (NIOX MINO) is used. The hand-held device shows good repeatability, and it can be used successfully on adults and most children. The new hand-held device will enable the introduction of exhaled NO measurements into the primary health care.

Exposure to environmental tobacco smoke and sensitisation in children

Background: Exposure to environmental tobacco smoke (ETS) increases the risk of respiratory illness in children but data are inconclusive regarding the risk of IgE sensitisation. Objective: To elucidate whether exposure to smoking prenatally and/or postnatally is related to IgE sensitisation in children at 4 years of age. Methods: As part of a prospective birth cohort study (BAMSE), a total of 4089 families with children answered questionnaires when the child was 2 months, 1, 2 and 4 years old on environmental factors and symptoms of allergic disease. Blood collected at age 4 years from 2614 children was analysed for IgE antibodies to common inhalant and food allergens. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression with adjustments for potential confounders. Results: There was no evident association between maternal smoking during pregnancy and risk of IgE sensitisation. In contrast, a dose–response effect was found for exposure to ETS from parental smoking during the first few months of life and IgE sensitisation. There was an increased risk of sensitisation to inhalant and/or food allergens (ORadj 1.28 (95% CI 1.01 to 1.62)) among children exposed to ETS at 2 months of age. The risk appeared particularly elevated for indoor inhalant allergens, such as cat (ORadj 1.96 (95% CI 1.28 to 2.99)) and for food allergens (ORadj 1.46 (95% CI 1.11 to 1.93)). The IgE sensitising effect of ETS seemed to be confined to infants of parents without allergic diseases and to ETS exposure during early infancy. Conclusions: Our data indicate that exposure in early infancy to ETS increases the risk of IgE sensitisation to indoor inhalant and food allergens.

Indoor exposures and recurrent wheezing in infants: a study in the BAMSE cohort

Aim: The aim of this study was to examine the relationship between indoor exposures and the home environment, and the development of recurrent wheezing during infancy. Methods: A birth cohort, comprising 4089 children, was followed. Information on exposures was obtained shortly after birth, and episodes of wheezing were recorded when the infants were 1 and 2 y of age. In a nested case‐control study, 181 infants were enrolled, who had three or more reported episodes of wheezing after 3 mo of age combined with either use of inhaled steroids or symptoms of bronchial hyper‐reactivity, and 359 age‐matched controls. Home inspections were performed during the winter following enrolment, and indoor conditions were measured. Results: Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. The OR for recurrent infant wheezing associated with signs of dampness reported prospectively by parents was 1.4 (0.9–2.2), and the OR for observed signs of dampness at home inspections was 1.6 (1.0–2.5). A trend was found in the risk of recurrent wheezing in relation to the number of indicators of dampness: OR 1.3 (0.8–2.2) for one sign of dampness and OR 2.7 (1.3–5.4) for three or more signs of dampness. Newly painted surfaces in the childs bedroom was associated with an increased OR for recurrent wheezing: 1.7 (1.3–2.6).

Nitric Oxide Airway Diffusing Capacity and Mucosal Concentration in Asthmatic Schoolchildren

Asthmatic patients show increased concentrations of nitric oxide (NO) in exhaled air (Feno). The diffusing capacity of NO in the airways (Dawno), the NO concentrations in the alveoli and the airway wall, and the maximal airway NO diffusion rate have previously been estimated noninvasively by measuring Feno at different exhalation flow rates in adults. We investigated these variables in 15 asthmatic schoolchildren (8–18 y) and 15 age-matched control subjects, with focus on their relation to exhaled NO at the recommended exhalation flow rate of 0.05 L/s (Feno0.05), age, and volume of the respiratory anatomic dead space. NO was measured on-line by chemiluminescence according to the European Respiratory Societys guidelines, and the NO plateau values at three different exhalation flow rates (11, 99, and 382 mL/s) were incorporated in a two-compartment model for NO diffusion. The NO concentration in the airway wall (p < 0.001), Dawno (p < 0.01), and the maximal airway NO diffusion rate (p < 0.001) were all higher in the asthmatic children than in control children. In contrast, there was no difference in the NO concentration in the alveoli (p = 0.13) between the groups. A positive correlation was seen between the volume of the respiratory anatomic dead space and Feno0.05 (r = 0.68, p < 0.01), the maximal airway NO diffusion rate (r = 0.71, p < 0.01), and Dawno (r = 0.56, p < 0.01) in control children, but not in asthmatic children. Feno0.05 correlated better with Dawno in asthmatic children (r = 0.65, p < 0.01) and with the NO concentration in the airway wall in control subjects (r < 0.77, p < 0.001) than vice versa. We conclude that Feno0.05 increases with increasing volume of the respiratory anatomic dead space in healthy children, suggesting that normal values for Feno0.05 should be related to age or body weight in this age group. Furthermore, the elevated Feno0.05 seen in asthmatic children is related to an increase in both Dawno and NO concentration in the airway wall. Because Dawno correlates with the volume of the respiratory anatomic dead space in control subjects and Feno0.05 correlates with Dawno in asthmatic children, we suggest that Dawno partly reflects the total NO-producing surface area and that a larger part of the bronchial tree produces NO in asthmatic children than in control children.

Oral bacteria--the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis.

BACKGROUND Nitrite in exhaled breath condensate (EBC) has been shown to be elevated in cystic fibrosis (CF), while exhaled nitric oxide (FENO) is paradoxically low. This has been argued to reflect increased metabolism of NO while its diffusion is obstructed by mucus. However, we wanted to study the possible influence of salivary nitrite and bacterial nitrate reduction on these parameters in CF patients by the intervention of an anti-bacterial mouthwash. METHODS EBC and saliva were collected from 15 CF patients (10-43 years) and 15 controls (9-44 years) before and 5 min after a 30s chlorhexidine mouthwash, in parallel with measurements of FENO. Nitrite and nitrate concentrations were measured fluorometrically. RESULTS EBC nitrite, but not nitrate, was significantly higher in the CF patients (median 3.6 vs 1.3 microM in controls, p<0.05) and decreased after mouthwash in both groups (3.6-1.4 microM, p<0.01; 1.3-0.5 microM, p<0.01). Salivary nitrite correlated significantly to EBC nitrite (r=0.60, p<0.001) and decreased correspondingly after chlorhexidine, whereas salivary nitrate increased. FENO was lower in CF and the difference between patients and controls was accentuated after mouthwash (5.4 vs 8.4 ppb in controls, p<0.05). CONCLUSION EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.

Wheezing bronchitis in children. Incidence, viral infections, and other risk factors in a defined population

Risk factors for severe wheezing bronchitis were studied in children aged 4 months to 4 years in need of hospitalization. The children included in the study consisted of all cases generated from a geographically defined population, the catchment area of St Görans hospital in Stockholm, The incidence was 3/1000 children and year, during the two years of observation, with the highest rate in boys under the age of 18 months (4. 7/1000). Symptoms of a preceding upper respiratory tract infection were reported in 90% of the cases, but a viral etiology could only be demonstrated with virus isolation in 26%. Respiratory syncytial virus was the most common finding in younger children. Rhinovirus was primarily seen in older children with a history of previous wheezing. Regardless of whether the cases had a positive or negative virus isolation they showed the same seasonal distribution. Furthermore, there was no difference in risk factors between children with a positive and negative virus isolation. Children older than 18 months with negative virus isolation had higher IgE levels than those with positive isolation, suggesting that atopy is of greater importance in this group.

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.

Evaluation of Exhaled Nitric Oxide in Schoolchildren at Different Exhalation Flow Rates

Nitric oxide (NO) in exhaled air is believed to reflect allergic inflammation in the airways. Measured levels of exhaled NO vary with the exhaled flow rate, which therefore must be standardized. The aim of this study was to estimate the optimal exhalation flow rate when measuring NO in exhaled air. We studied 15 asthmatic children (8-18 y) with elevated NO levels and 15 age-matched controls and focused on how the quality of the NO curve profile, the discriminatory power, and the reproducibility were influenced by the exhalation flow rate. We used an on-line system for NO measurements at six different exhalation flow rates in the interval of 11-382 mL/s. The fraction of exhaled nitric oxide (FENO) was highly flow-dependent as was expected. Intermediate flow rates yielded a flat and stable NO plateau and were considerably easier to interpret than those obtained at the highest and lowest flow rates. The ratio of FENO between asthmatics and controls was lower at higher flow rates and a considerable overlap in NO values was demonstrated at all flow rates except 50 mL/s. The reproducibility was much lower at more extreme flow rates and was best at 50 mL/s. We conclude that a target exhalation flow rate of approximately 50 mL/s is to be preferred using the single-breath method for on-line NO measurements in schoolchildren.

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.

Parental smoking increases the risk for eczema with sensitization in 4-year-old children

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