Obesity and Asthma: Key Clinical Questions.

Obesity is a common comorbidity of asthma that is associated not only with development of the disease, but also with poorer disease control and greater severity. Recent prospective evidence supports the idea that body weight gain precedes the development of asthma, although the debate is far from over. The objective of this document is to conduct a systematic review of 3 clinical questions related to asthma and obesity: (a) Obesity and asthma: the chicken or the egg? Clinical insights from epidemiological and phenotyping studies. (b) Is obesity a confounding factor in the diagnosis and management of asthma, especially in severe or difficult-to-control asthma? (c) How do obese asthma patients respond to pharmacological treatments and to biological drugs? Do we have effective specific interventions? Revised epidemiological, pathological, and mechanistic evidence combined with data from interventional clinical trials prevent us from clearly stating that obesity causes asthma. However, the complexity and heterogeneity of both illnesses make several clinical scenarios possible. Furthermore, asthma represents an additional clinical challenge in the obese patient. Physicians need to be aware of the confounding effects created by the more marked perception of symptoms, alterations in lung function, and the various comorbidities that obese persons present. Exhaustive phenotyping of the obese asthma patient should enable us to develop a rational therapeutic plan, including both the pharmacological approach and specific antiobesity therapies such as combining diet and exercise and, in extreme cases, bariatric surgery.

Referral Criteria for Asthma: Consensus Document.

Asthma is one of the most prevalent chronic diseases in Spain. Current treatments ensure that the disease is controlled in most cases. However, disease is often uncontrolled in daily clinical practice, mainly owing to underdiagnosis, loss to follow-up, and poor adherence to therapy. In order to improve this situation, we must coordinate all those health professionals who intervene in patient care. Therefore, the Spanish Society of Allergology and Clinical Immunology (SEAIC), the Spanish Society of Primary Care Physicians (SEMERGEN), the Spanish Society of Family and Community Medicine (semFYC), the Spanish Society of General and Family Physicians (SEMG), and the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) have drawn up a consensus document in which they establish criteria for referral and guidelines for the diagnosis, control, and follow-up of patients with asthma. The document aims to facilitate continuing and improved care in this area.

Impact of Specific Training in Anaphylaxis for Triage Nursing Staff in the Pediatric Emergency Department of a Tertiary Hospital.

BACKGROUND: After a diagnosis of anaphylaxis, patients receive action management plans to prevent and treat new episodes, including attending the emergency department for follow-up or further treatment. In a previous study, we observed that more than half of the children with anaphylaxis were incorrectly prioritized in our Pediatric Emergency Unit (PEU), thus delaying their treatment. In conjunction with our PEU staff, we designed a basic educational intervention (BEI) to try to solve this problem. We analyzed the effect of the intervention on triage of children subsequently diagnosed with anaphylaxis. METHODS: Our BEI consisted of a training lecture given to the PEU triage nurses and the design of a reference card highlighting symptoms and risk factors of anaphylaxis. We included 138 children with a medical diagnosis of anaphylaxis and assessed modifications in their triage priority level and waiting times (WT) before seeing a physician after our intervention. According to the BEI implementation date, 69 children were diagnosed before the intervention (G1) and 69 after (G2). Clinical data were compared to assess the severity of the episodes. RESULTS: There were no differences between the groups. WT decreased (from 8 to 1 minute; P=.03), and the number of correctly identified patients increased after the BEI (36.2% [G1] and 72.2% [G2]; P=.0001). CONCLUSIONS: Our BEI was effective, improving the identification and prioritization of children with anaphylaxis and reducing their WT. We need to pay attention to the functioning of our patients' reference emergency department and establish interdisciplinary measures that enable optimal management of anaphylaxis.

Cutoff point for exhaled nitric oxide corresponding to 3% sputum eosinophils.

BACKGROUND: The eosinophilic asthma phenotype (sputum eosinophils 3%) indicates a good response to corticosteroids and T(H)2 immunomodulators. Exhaled nitric oxide (FeNO) is rapidly measured by portable devices, and although it is not a selective marker of eosinophilic inflammation, several studies have demonstrated a strong correlation with it. We investigated which FeNO value was the best fit with 3% sputum eosinophils in asthma patients. METHODS: We included 129 consecutive, nonsmoking asthmatics who underwent skin tests, FeNO quantification (NIOX MINO), spirometry, and induced sputum analysis and completed the Asthma Control Test questionnaire. Receiver operating characteristic curves were constructed, and logistic regression analysis was performed. RESULTS: Symptoms were detected more frequently in the eosinophilic asthma group, as were higher airway obstruction and sensitivity to hypertonic saline. The FeNO cutoff point of 21 ppb was the best fit with 3% sputum eosinophilia. This value behaved better among corticosteroid-naïve patients (sensitivity, 97%; specificity, 58%; positive predictive value, 86%; negative predictive value, 88%) than among those receiving corticosteroids (sensitivity, 81%; specificity, 25%; positive predictive value, 74%; negative predictive value, 33%). CONCLUSION: FeNO ≥ 21 ppb is associated with airway eosinophilia. In corticosteroid-naïve patients, FeNO < 21 ppb enables us to rule out airway eosinophilia.

Mannitol versus hypertonic saline: Safety and efficacy of mannitol and hypertonic saline in sputum induction and bronchial hyperreactivity assessment.

Eosinophilic asthma phenotype predicts good response to corticosteroids and associates to asthmatic exacerbations. Sputum induction by hypertonic saline (HS) inhalation is technically demanding. Bronchial hyperresponsiveness (BHR) to osmotic agents indirectly mirrors active airway inflammation. We compared the safety and ability of HS and mannitol to induce sputum and measure BHR. We evaluated the stability of inflammatory phenotypes. We studied 35 non-smoking asthmatics randomized to undergo HS and mannitol challenges on 2 days 1 week apart. Sputum was sampled for cell analysis and phenotyped as eosinophilic (≥3% eosinophils) and non-eosinophilic (<3%) asthma. Nineteen subjects had BHR to mannitol and nine of them also had BHR to HS. Drops in forced expiratory volume in 1 s were higher from HS challenge than from mannitol challenge. Adequate sputum samples were obtained from 80% subjects (68% mannitol and 71% HS). Eosinophils and macrophages from both challenges correlated. Neutrophils were higher in sputum from HS. Ninety percent samples were equally phenotyped with HS and mannitol. Fractional exhaled nitric oxide, sputum eosinophils and BHR correlated in both challenges. HS and mannitol showed similar capacity to produce valuable sputum samples. BHR to both osmotic stimuli partially resembled airway eosinophilic inflammation but mannitol was more sensitive than HS to assess BHR. Eosinophilic phenotype remained stable in most patients with both stimuli.

Spirometric and exhaled nitric oxide reference values in preschool children from the community of Navarra.

BACKGROUND AND OBJECTIVE: Preschool children can perform quality, reproducible spirometric maneuvers, provided appropriate equipment is used and specially trained nursing staff training are available. However, use of spirometry for the diagnosis and follow-up of preschool children with respiratory diseases remains limited in clinical practice, because consensus on test quality and acceptability criteria and reference data are lacking. We initiated the present study with the aim of developing reference equations, since tables of normal values for this age group are not available in our area. PATIENTS AND METHODS: The study population comprised healthy preschool children in our community. Normal values for exhaled nitric oxide in this age range were assessed. Regression equations were constructed using univariate and multivariate models. RESULTS: A total of 114 healthy preschool children aged 3 to 6 years were enrolled. According to the criteria of the American Thoracic Society/European Respiratory Society, 60 children were able to perform acceptable and reproducible spirometric maneuvers. The best correlations were observed for the untransformed linear regression model that included height. The correlation coefficients for forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV0.5 were 0.89, 0.88, and 0.86, respectively. The regression equations for the calculation of reference values were as follows: FVC = -2.6 + 0.036 x height, cm FEV1 = -2.04 + 0.029 x height, cm FEV0.5 = -1.53 + 0.022 x height, cm. We obtained fraction of inhaled nitric oxygen (FeNO) values for 56 children. The mean (SD) value was 11 (4.9) ppb. CONCLUSIONS: Most preschool children in our area were able to perform quality spirometry maneuvers. We obtained regression equations that allowed us to calculate the reference ranges in our population and the distribution of normal FeNO values.

Duration of asthma and lung function in life-long nonsmoking adults.

BACKGROUND: The airways of adult or elderly asthmatics are likely candidates for airway remodeling, resulting in persistent airflow obstruction. This population can provide a good model for cross-sectional evaluation of the effect of asthma duration on airflow. METHODS: We evaluated postbronchodilator airflow and lung volumes at baseline and after a short course of oral prednisone in a group of 42 never-smokers with persistent mild or moderate asthma aged 55 years or older. Patients were grouped as having short duration asthma (SDA, <14 years) or long duration asthma (LDA, > or =14 years) according to the median duration of the disease (14 years) of the sample. RESULTS: There were no significant differences in patient characteristics or asthma severity indices between the groups. After a short course of prednisone, forced expiratory volume in 1 second (FEV1) and the ratio of FEV to forced vital capacity (FVC) were significantly higher for the SDA group. Only 3 patients presented persistent airflow limitation (FEV1/FVC% < 75%). An inverse correlation was demonstrated between duration of asthma and postbronchodilator FEV1 (% predicted) (r = -0.43, P = .01) and FEV1/FVC% (r = -0.50, P = .003). CONCLUSION: Our data show a close relationship between duration of disease and loss of lung function, supporting the concept of asthma as a slow, progressive disease at least among those patients with a mild-to-moderate severity. Permanent airflow obstruction in mild or moderate asthma is unusual, but can occur in a small number suffering from the disease for years.

Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis.

BACKGROUND: Sublingual route, that allows the safe administration of allergen vaccination at home and without injections, is a highly attractive alternative to parenteral delivery, especially among the youngest population. However, its efficacy in children has been questioned. OBJECTIVE: To evaluate the efficacy (symptom and medication scores) of sublingual allergen vaccination compared to placebo in paediatric patients. SEARCH STRATEGY: MEDLINE, EMBASE, ISI and the Cochrane Central Register of Controlled Trials were explored (completed in January/04) for potentially relevant studies. SELECTION CRITERIA: Randomized double-blind placebo-controlled clinical trials involving children < or = 14 years-old with either rhinitis or asthma of proved allergic aetiology. Data collection and analysis. Two reviewers analyzed independently the eligibility of studies for inclusion. The combined standardized mean difference (SMD) method was used to evaluate differences. Since heterogeneity was expected, probably due to the different procedures from each trial, we used the random effect model to obtain SMD. However, we also present the SMD values from the fixed effect model. The main outcomes were clinical symptom (asthma, rhinitis and conjunctivitis) and drug requirement scores. Safety, immunological and clinical changes were also reviewed. RESULTS: Seven double-blind placebo-controlled trials, enrolling 256 children (129 treatment and 127 placebo recipients), were analyzed. We observed decreases in symptom (SMD: -1.42 for asthma, -0.44 for rhinitis and -1.49 for conjunctivitis) and medication requirement (SMD: -1.01) scores. Only reductions in asthma (p=0.01) and drug dosage (p=0.06) scores reached statistical significance with the random effect model but changes in rhinitis symptoms (p=0.27) or conjunctival symptoms (p=0.19) were not statisticaly significant. Results obtained with the fixed effect model were similar in magnitude (SMD: -1.60 for asthma, SMD: -0.47 for rhinitis, SMD: -1.09 for conjunctivitis and, SMD: -0.54 for drug intake). Safety was a constant in all the studies; neither severe nor systemic reactions were observed and, oral and gastrointestinal complains were the most common adverse effects. CONCLUSION: In children, sublingual delivery of allergen vaccination constitutes a safe and effective alternative to the sublingual route to reduce allergy respiratory symptoms and drug intake. Further studies in this group of age are required to establish the optimal conditions for sublingual allergen vaccination.

Comparative analysis of the bronchodilator response measured by impulse oscillometry (IOS), spirometry and body plethysmography in asthmatic children.

BACKGROUND: Asthma is common among young children. The assessment of respiratory resistance by the impulse oscillometry system (IOS), based on the superimposition of respiratory flow by short-time impulses, requires no patient active collaboration. AIM: We evaluated the baseline repeatability and bronchodilator response of IOS indices in preschool children, their correlation with spirometry and whole body plethysmography, and differences between atopic and nonatopic children. PATIENTS AND METHODS: Thirty-three asthmatic children (3-6 yrs.) underwent IOS measurement (R5rs, R20rs and X5rs) by triplicate at the baseline, after placebo and after salbutamol inhalation. Spirometry (FEV1) and whole body plethysmography (sRaw) were made at the baseline and after salbutamol. Baseline within-test (coefficient of variation: CV%) and between-test repeatability (baseline-placebo) were addressed. Bronchodilator response was evaluated by the SD index (change in multiples of the between-test repeatability). RESULTS: Baseline repeatability for R5rs was 4.1%. Its values decreased by 2SD after salbutamol inhalation, and correlated with FEV1 and sRaw at both, baseline (r=-0.51 and r=0.49) and post-salbutamol (r=-0.63 and r=0.54). A trend towards correlation between salbutamol-induced changes in R5rs and in sRaw (r=0.33) was observed. Atopic and non-atopic children showed no differences in lung function. CONCLUSION: IOS was well accepted by young asthmatic children and provided reproducible and sensitive indices of lung function. Resistance values obtained by IOS at low frequency (R5rs) were reproducible and correlated with spirometry and plethysmographic values.

Determinants of allergen-induced late bronchial responses in mild asthmatics.

STUDY OBJECTIVE: To examine the baseline factors influencing the occurrence and magnitude of immediate- and late-phase responses in asthmatic patients after an allergen-induced bronchial provocation test (A-BPT). DESIGN: Cross-sectional analysis in a homogenous group of 31 mild, Dermatophagoides pteronyssinus-allergic patients with asthma. SETTING: Allergy Department, Hospital Virgen del Camino, Pamplona, Spain. INTERVENTIONS AND MEASUREMENTS: Patients completed an asthma symptom questionnaire and underwent skin tests, sputum induction, and methacholine bronchial provocation test. The A-BPT was performed on a separate day. Sputum cell profile and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin-5 levels were quantified in the entire sputum supernatant. Assays were done for eosinophils in blood, and/or ECP, and total and specific IgE levels in serum. Exposure to D pteronyssinus major allergens (Der p1 and Der 2) was measured by an assay based on monoclonal antibodies. RESULTS: A-BPT findings were positive in all patients, and late-phase responses were detected in 29%. Late responders were exposed to higher levels of Der p1 (p = 0.028), had greater levels of ECP (p = 0.007) and albumin (p = 0.019) in sputum, and showed a trend toward higher lymphocyte numbers (p = 0.053) in sputum than isolated early responders. The allergen-induced provocative dose that induced a fall in FEV(1) values > or =20% from the postdiluent values correlated with bronchial hyperresponsiveness (r = 0.36). The late-phase response magnitude correlated with Der p1 exposure (r = 0.49) and showed a trend toward correlation with sputum ECP levels (r = 0.38). CONCLUSION: Factors involved in the development of allergen-induced immediate- and late-phase responses are different. Allergen natural exposure might prime the infiltration of the airway by activated inflammatory cells enhancing the appearance and the severity of late-phase responses.

Discriminant analysis in allergic rhinitis and asthma: methacholine dose-response slope allows a good differentiation between mild asthma and rhinitis.

Asthma and rhinitis frequently coexist in allergic patients, but nasal symptoms may predominate, leading to asthma underdiagnosis and undertreatment. Discriminant analysis obtains the best differentiation between groups using one or one set of variables. Our aim was to identify the laboratory test [allergen exposure, total and specific serum IgE, lung function, blood eosinophils and, bronchial response and sensitivity to methacholine (Mth) and allergen] or combination of them that allowed the best differentiation between mild asthma and allergic rhinitis. A cross-sectional analysis was performed in 86 Dermatophogoides pteronyssinus allergic rhinitis patients, who were classified according to clinical data as rhinitis plus mild asthma (n = 62) or "pure" rhinitis (n = 24). Bronchial symptoms had been exhaustively evaluated during a 2-years pre-inclusion period. Patients underwent skin tests and bronchial challenge with Mth and allergen. The exposure to D. pteronyssinus allergen (Der pl) was quantified in dust samples. Dose-response curves with Mth [until the FEV1 fell by 40% or the maximal dose (200 mg/ml) was inhaled] were attained. We developed multiple models of discriminant analysis in order to evaluate the capacity of the above variables to differentiate groups. Asthma patients had higher total and specific IgE levels and a greater sensitivity (PD20 values) and response [dose-response slope (DRS)] to both Mth and allergen. The model entering these variables was the one that correctly classified more patients (79.2%). The discriminative power of the model that only included Mth-DRS values was similar to the above (78.8%). Bronchial response to Mth is quantitatively different in allergic rhinitis patients who display mild asthma symptoms when compared to those that only report rhinitis, suggesting a distinct bronchial intrinsic behavior. The utilization of complete dose-response curves with Mth allows a good separation between mild asthma and "pure" rhinitis patients and might be useful in the diagnosis of mild asthma. Whether the early detection and treatment of these patients prevents the development of symptomatic asthma needs further evaluation.

Analysis of induced sputum: a new approach to the study of airway inflammation in asthma.

Induced sputum is a simple method that enables the analysis of lower respiratory tract material obtained through non-invasive methods. Validation of the technique for the study of airway inflammation in asthma and other respiratory diseases, together with the most relevant findings reported in the literature, are reviewed herein. Accurate methods that can be applied to the analysis of induced sputum samples, such as immunocytochemistry, flow cytometry or polymerase chain reaction are also discussed.

[Spirometry quality in preschool children]. / Calidad de la espirometría en preescolares.

BACKGROUND: Carrying out quality spirometric maneuvers in preschool children in both the diagnosis and follow-up of respiratory diseases continues to be very scarce. This is due to several reasons, including a lack of consensus on quality criteria and the acceptability of the test. The purpose of this study is therefore to obtain reference norms from a population of healthy preschool children from the Autonomous Community of Navarre (Spain). METHOD: A total of 114 healthy preschool children aged between 3 and 7 years of age, without prior experience in carrying out lung function tests, were included. RESULTS: A total of 76 were able to realize at least two acceptable spirometric maneuvers, and 60 of them maneuvers that were acceptable and reproducible, according to ATS/ERS criteria. This represents a global success percentage of 59%. The most common failing was premature and brusque termination of the spirometric maneuver, followed by an inadequate peak in breathing. CONCLUSIONS: Over half of the preschool children were able to realize quality spirometric maneuvers. Our data make it possible to recommend the proposed quality criteria as being suitable for routine use, and to encourage the use of spirometry in regular clinical practice within the setting of specialized care.