Comorbidities of chronic rhinosinusitis in children and adults.

BACKGROUND: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nose and paranasal sinuses lasting ≥12 weeks. CRS may exist with (CRSwNP) or without (CRSsNP) nasal polyps. The aim was to evaluate conditions associated with CRS in a randomized hospital cohort. We hypothesized that comorbidities and surgical procedures differ between pediatric and adult patients. METHODS: This study consisted of hospital registry data of a random sample of rhinosinusitis patients (age range 0-89 years) with the diagnosis of J32 or J33, correspondingly, registered during outpatient visits from 2005 to 2019 (n = 1461). The covariates of interest were collected from electronic health records based on ICD-10 codes and keyword searches. RESULTS: Among pediatric patients (n = 104), the relative proportions of CRSsNP and CRSwNP were 86% and 14% respectively. The relative proportions of adult patients (n = 1357) with CRSsNP and CRSwNP were 60% and 40%, respectively. The following comorbidities significantly differed (p < 0.05) between pediatric and adult populations: allergy, chronic otitis media, and tonsillar diseases. In total, 41 % of the children and 46% of the adults underwent baseline endoscopic sinus surgery (ESS). Additional surgeries of the ear, nose and pharynx were significantly more common among children compared with adults. Risk of revision after baseline ESS was associated (p < 0.05) with allergy, asthma, eosinophilia, CRSwNP, immunodeficiency or its suspicion, non-steroidal anti-inflammatory drug exacerbated respiratory disease, and number of any diseases ≥2. CONCLUSIONS: Our study showed that comorbidities differ between pediatric and adult rhinosinusitis patients, as allergy, asthma and allergy, chronic otitis media, mental health disorders, and tonsils disease were significantly more prevalent among pediatric patients. Children and adults were equally treated with ESS. Notably, children underwent additional surgery on adenoids and tonsils more frequently. The effectiveness of ESS in multimorbid adults should be assessed at an individual level.

Radiological score of computed tomography scans predicts revision surgery for chronic rhinosinusitis.

Objective: Evaluate computed tomography (CT) signs that predict need for revision endoscopic sinus surgery (ESS) of chronic rhinosinusitis (CRS). Methods: CRS patients (n = 48) underwent routine sinus CT scans and baseline ESS in 2006-2011. Lund-Mackay (LM) scores and 43 other CT signs were analysed blinded from both sides. Patients filled in a questionnaire during the day of CT scanning. Follow-up data were collected from hospital records until January 2018. Associations were analysed by Fisher's exact, Mann Whitney U, Kaplan-Meier method with logrank test and Cox's proportional hazard model. Results: Total LM score was not significantly associated with the need for revision ESS. The best predictive model was a sum of CT signs of non-detectable anatomy of inferior/middle turbinates, obstructed frontal recess, and previous sinus surgery. Using these CT findings, we formed a Radiological Score (RS) (min-max, 0-3 points). Having at least one RS point was significantly associated with the need for revision ESS during the average follow-up of 10.7 years (p = 0.008, Logrank test). Conclusion: We identified a radiologic score that was able to predict the need for revision ESS, which is probably useful in predicting CRS outcomes.

The Finnish Allergy Program 2008-2018: Society-wide proactive program for change of management to mitigate allergy burden.

A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education.

A comparison of biologicals in the treatment of adults with severe asthma - real-life experiences.

BACKGROUND: Anti-IgE (omalizumab) and anti-IL5/IL5R (reslizumab, mepolizumab and benralizumab) treatments are available for severe allergic and eosinophilic asthma. In these patients, studies have shown beneficial effects in oral corticosteroid use and exacerbations. The aim of this retrospective single-center study was to evaluate the effect of biological therapy on severe asthma and to compare different therapies. METHODS: We collected and analysed results of anti-IL5/IL5R and anti-IgE therapies for asthma from January 2009 until October 2019 in specialized care. We compared number of exacerbations, asthma symptoms and use of per oral corticosteroids and antimicrobics because of asthma before and during biological therapy, and in a separate analysis need for per oral corticosteroids, antimicrobics or surgery due to upper respiratory tract diseases in asthmatics receiving biologicals. The analyses were done using the Chi square test, T-test or Mann-Whitney U -test, the Kruskall-Wallis test or the Wilcoxon test. RESULTS: Of 64 patients, 40 used continuous per oral corticosteroid therapy prior to biological therapy. The mean daily dose of per oral corticosteroid was reduced in those with anti-IL5/IL5R therapy (- 3.0 mg, p = 0.02). The number of annual per oral corticosteroid courses decreased in both the anti-IL5/IL5R (- 2.8 courses, p < 0.05) and anti-IgE groups (- 1.3 courses, p < 0.05). The number of annual antibiotic courses (- 0.7 courses, p = 0.04) and total number of exacerbation events (- 4.4 events/year, p < 0.05) were reduced in the anti-IL5/IL5R group. In the 55 asthma patients analysed for upper respiratory tract findings, the results suggested a reduction in need for chronic rhinosinusitis surgery during biological therapy. CONCLUSIONS: Results with biological therapies in this real-life clinical setting are comparable to those reported in clinical trials. Biological therapy reduces exacerbations and per oral corticosteroid use. TRIAL REGISTRATION: NCT04158050, retrospectively registered 6.11.2019.

Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze.

BACKGROUND: The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. OBJECTIVE: To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. METHODS: Inclusion criteria were as follows: full-term, 3-23 months of age; doctor -diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. RESULTS: Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (P = .031). CONCLUSIONS AND CLINICAL RELEVANCE: These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.

Multimorbidity in Asthma, Allergic Conditions and COPD Increase Disease Severity, Drug Use and Costs: The Finnish Pharmacy Survey.

BACKGROUND: Asthma, allergic conditions, and COPD overlap, but the effect of them and their combinations on disease severity, need for drugs, use of healthcare, and costs is poorly known. OBJECTIVE: To study how different allergic diseases co-occur in asthma and allergy patients and evaluate the use of medication well as drug and healthcare costs. METHODS: Nationwide Allergy Barometer Survey was carried out in the Finnish pharmacies during 1 week in September 2016. Altogether, 956 patients (5-75 years) who purchased asthma or allergy drugs with prescription participated in 351 pharmacies. RESULTS: Of the participants, 78% reported physician-diagnosed asthma, 57% allergic rhinitis, 24% atopic eczema, 21% food allergy, 20% allergic conjunctivitis, 8% anaphylaxis, and 8% COPD. One-third of the patients had at least three conditions, and multimorbidity was common across all age groups. Disease severity increased with the number of coexisting conditions, and asthma severity also with age. Patients with asthma alone used on average 3.8 drugs with the annual costs of EUR 661. This increased to 4.9 drugs and EUR 847 in asthmatics with multimorbidity. For all participants, costs of drugs and healthcare services together during the preceding year were on average EUR 1,214, of which 56% were drug costs. The costs doubled to EUR 2,714 in 65 subjects (7%) who had both asthma and COPD. CONCLUSIONS: In asthma and allergy, multimorbidity and polypharmacy are major concerns. Disease severity, drug use, and costs increased with multimorbid conditions. To reduce the burden, allergy management should be better integrated and more comprehensive.

Primary Prevention of Airway Allergy.

PURPOSE OF REVIEW: The aim of this paper is to review and summarize the current knowledge of prevention of airway allergy. RECENT FINDINGS: Allergic rhinitis and asthma are allergic airway diseases. Due to their increasing incidence and socioeconomic burden, allergic airway diseases have recently gained attention worldwide. The primary prevention of allergic airway diseases focuses on offspring's gestational and childhood environment, such as maternal smoking and diet during pregnancy and breastfeeding as well as exposure to environmental microbes and irritants. SUMMARY: Asthma and allergic rhinitis are a major public health problem worldwide. They have increasing prevalence and thus attempts to their prevention are mandatory. Rapid action needs to be taken to restrain smoking among children and adolescents in order to prevent burden of allergic airway diseases. Exposure to pollution and environmental issues concerning hygiene and lifestyle would also need to be actively addressed. More evidence is still needed in order to draw linings concerning maternal diet and other factors during the offspring's whole life span.

Monocytes accumulate in the airways of children with fatal asthma.

BACKGROUND: Activated T helper type 2 (Th2) cells are believed to play a pivotal role in allergic airway inflammation, but which cells attract and activate Th2 cells locally have not been fully determined. Recently, it was shown in an experimental human model of allergic rhinitis (AR) that activated monocytes rapidly accumulate in the nasal mucosa after local allergen challenge, where they promote recruitment of Th2 cells and eosinophils. OBJECTIVE: To investigate whether monocytes are recruited to the lungs in paediatric asthma. METHODS: Tissue samples obtained from children and adolescents with fatal asthma attack (n = 12), age-matched non-atopic controls (n = 9) and allergen-challenged AR patients (n = 8) were subjected to in situ immunostaining. RESULTS: Monocytes, identified as CD68+S100A8/A9+ cells, were significantly increased in the lower airway mucosa and in the alveoli of fatal asthma patients compared with control individuals. Interestingly, cellular aggregates containing CD68+S100A8/A9+ monocytes obstructing the lumen of bronchioles were found in asthmatics (8 out of 12) but not in controls. Analysing tissue specimens from challenged AR patients, we confirmed that co-staining with CD68 and S100A8/A9 was a valid method to identify recently recruited monocytes. We also showed that the vast majority of accumulating monocytes both in the lungs and in the nasal mucosa expressed matrix metalloproteinase 10, suggesting that this protein may be involved in their migration within the tissue. CONCLUSIONS AND CLINICAL RELEVANCE: Monocytes accumulated in the lungs of children and adolescents with fatal asthma attack. This finding strongly suggests that monocytes are directly involved in the immunopathology of asthma and that these pro-inflammatory cells are potential targets for therapy.

Health care resource utilization and characteristics of patients with eosinophilic asthma in secondary health care in Finland.

Background: Eosinophilic airway inflammation is common in asthma patients and appears to be associated with severe exacerbations and loss of asthma control. Objective: To describe the resource utilization and clinical characteristics of patients with eosinophilic asthma. Design: Asthma patients ≥18 years with ≥1 blood eosinophil count in secondary care (South West Finland) during 2003‒2013 were included. Clinical characteristics (age, lung function, body mass index, and comorbidities) and asthma-related resource utilization (hospital admissions, outpatient visits, and emergency room [ER] visits) were retrieved. Resource utilization rates were compared for patients with blood eosinophil ≤ or >300 cells/µL, using adjusted negative binomial regression models. Results: Overall, 4,357 eligible patients were identified (mean age 60 years, females 68%), of which 1,927 (44%) had >300 eosinophil cells/µL blood. Patients with ≤300 and >300 eosinophil counts, exhibited similar clinical characteristics, including advanced age, poor lung function, and overweight. Comorbidities such as pneumonia, sinusitis, and nasal polyps, were more frequent among those with >300 eosinophil cells/µL blood compared with patients with lower counts. Eosinophil counts >300 cells/µL were associated with greater hospital admissions (rate ratio [RR] [95% confidence interval CI]: 1.13 [1.02;1.24]) and outpatient visits (RR [95% CI]: 1.11 [1.03;1.20]) compared with patients with lower eosinophil counts. Rates of ER visits were similar between the patient groups (RR [95% CI]: 0.99 [0.87;1.12]). Conclusions: Hospital admissions and outpatient visits occurred more often for patients with eosinophil counts >300 cells/µL, than for patients with lower eosinophil counts. Routine blood eosinophil screening might be useful to identify patients with an eosinophilic phenotype eligible for more targeted treatments.

Self-Reported Allergic Rhinitis and/or Allergic Conjunctivitis Associate with IL13 rs20541 Polymorphism in Finnish Adult Asthma Patients.

BACKGROUND: Our aim was to observe factors associated with IL13 rs20541 polymorphism and other factors with or without allergic comorbidities such as subject-reported allergic rhinitis (AR) and/or allergic conjunctivitis (AC) symptoms in adult asthmatics. METHODS: A population-based sample of Finnish adult asthma patients (n = 1,156) and matched controls (n = 1,792) filled in a questionnaire. Asthma was diagnosed based on a typical history of asthma symptoms and lung function tests. Skin prick tests with 17 aeroallergens and blood tests including analysis of interleukin 13 (IL13) rs20541 (G/A) genotypes were performed for a subsample (n = 193). RESULTS: The proportion of asthmatics reporting AR was 61.9% and reporting AC was 40.7%. After adjustments, the presence of the IL13 rs20541A- allele (OR 3.06, 95% CI 1.42-6.58, p = 0.004) or multisensitization (adjusted OR 4.59, 95% CI 1.48-14.26, p = 0.008) was associated with AR/AC asthma. Nasal polyps and acetylsalicylic acid-exacerbated respiratory disease was also associated with AR/AC asthma. CONCLUSIONS: Adult AR/AC asthma could putatively be a phenotype, characterized by the presence of atopic and/or eosinophilic factors and a high prevalence of the IL13 rs20541A- allele. Studies on the mechanisms behind this and in other populations are needed.

Sensitivity of newly defined impulse oscillometry indices in preschool children.

INTRODUCTION: Early origins of chronic obstructive pulmonary disease have been recognized. Impulse oscillometry (IOS) is suitable for assessment of lung function also in preschool children, and some novel indices have been connected to assessment of small airway function. However, limited data exist on the sensitivity of these new indices to detect lung function deficits in young symptomatic children. METHODS: IOS measurements of 103 healthy preschool children were evaluated to establish reference equations for the difference between respiratory resistance at 5 and 20 Hz (R5-20), the relative difference of R5-20 (R5-20%), and area under the reactance curve (AX). Thereafter, IOS results of children with late-onset troublesome lung symptoms (n = 20), a history of early wheeze (n = 37), or a history of bronchopulmonary dysplasia (BPD, n = 8) were compared to healthy children. RESULTS: None of the patient groups differed from healthy regarding respiratory resistance at 5 Hz (R5), and only children with a history of BPD differed from healthy regarding respiratory reactance at 5 Hz (X5). In contrast, z-scores of R5-20, R5-20%, and AX were significantly higher in all patient groups than in healthy children (P < 0.001), showing improved sensitivity (20-55%) compared to R5 and X5 (5-6%). CONCLUSION: R5-20, R5-20%, and AX are superior to conventional IOS parameters in distinguishing children with current or past lower respiratory tract symptoms from healthy, and may prove valuable for screening early lung function deficits. Pediatr Pulmonol. 2017;52:598-605. © 2016 Wiley Periodicals, Inc.

Factors affecting revision rate of chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a variable multifactorial disease. It can be divided into forms with nasal polyps (CRSwNP) and without (CRSsNP). Sinus and/or nasal polypectomy surgery are considered if maximal conservative treatment is insufficient. The predictive factors of the need of revision surgery comprise mostly the CRSwNP phenotype and are not fully understood. STUDY DESIGN: The aim of this follow-up study was to evaluate the factors associated with the revision surgery rate in CRS patients with variable extent of disease. METHODS: Data of CRS patients (N = 178) undergoing sinus surgery and/or nasal polypectomy in 2001 to 2010 were used. Patient characteristics and follow-up data were collected from patient records and questionnaires. Associations were analyzed by Fisher's exact, Mann Whitney U, and the Kaplan-Meier method with log-rank test. Unadjusted Cox's proportional hazard models were used for 12 variables and were fitted for the need for revision sinus surgery and/or nasal polypectomy during follow-up of in average 9 years. RESULTS: The proportion of CRS patients who had undergone revision in 5 years was 9.6%. After adjustment, the following factors associated significantly with the need for recurrent CRS surgery: allergic rhinitis, corticosteroid treatment, previous surgery of CRS, and recurrent NP. CONCLUSION: Increased risk of progressive CRS phenotypes with the need for revision surgery would putatively be recognized by relatively simple clinical questions. Further studies with increased sample size are needed to evaluate whether these predictive factors would be relevant for developing better detection and management of progressive CRS. LEVEL OF EVIDENCE: 2b.

Lung function, airway remodeling, and inflammation in infants: outcome at 8 years.

BACKGROUND: Associations between early deficits of lung function, infant airway disease, and outcome at school age in symptomatic infants are still unclear. OBJECTIVE: To report follow-up data on a unique cohort of children investigated invasively in infancy to determine predictive value of airway disease for school-aged respiratory outcomes. METHODS: Fifty-three infants previously studied using bronchoscopy and airway conductance were approached at 8 years of age. Symptoms, lung volumes, and airway responsiveness were reassessed. Data on lifetime purchase of asthma medication were obtained. Lung function was compared with that of 63 healthy nonasthmatic children. RESULTS: Forty-seven children were reevaluated. Physician-diagnosed asthma was present in 39 children (83%). Twenty-five children (53%) had current and 14 children (30%) had past asthma. No pathologic feature in infancy correlated with any outcome parameter. As expected, study children had significantly reduced lung function and increased airway responsiveness compared with healthy controls, and very early symptoms were risk factors for reduced lung function. Current asthma was associated with reduced infant lung function and parental asthma. Reduced lung function in infancy was associated with purchase of inhaled corticosteroids when 6 to 8 and 0 to 8 years of age. CONCLUSION: The lack of predictive value of any pathologic measure in infancy, reported here for the first time to our knowledge, demonstrates that pathologic processes determining the inception of asthma, which are as yet undescribed, are different from the eosinophilic inflammation associated with ongoing disease.

Assessing direct and indirect airway hyperresponsiveness in children using impulse oscillometry.

BACKGROUND: Airway hyperresponsiveness (AHR) is a hallmark of asthma but its assessment is usually restricted to older children who are capable of performing the maneuvers involved in spirometry. In younger children, a feasible option to perform the lung function measurement is impulse oscillometry (IOS), which requires less cooperation. OBJECTIVE: To evaluate whether assessment of AHR by IOS could differentiate children with various obstructive symptoms from one another. METHODS: One hundred twenty-one children (median age 6.0 years, range 3.7-8.1 years) were examined: 31 with probable asthma characterized by current troublesome lung symptoms, 61 with a history of early wheezing disorder (recurrent wheezing ≤24 months of age), 15 with a history of bronchopulmonary dysplasia, and 14 healthy controls. Indirect AHR was assessed by exercise and mannitol challenge tests, and direct AHR was assessed with methacholine using IOS. AHR to exercise was defined as an increase of at least 40% in respiratory resistance at 5 Hz. In the mannitol and methacholine challenges, the dose causing an increase of 40% in respiratory resistance at 5 Hz was calculated. RESULTS: AHR to exercise was good at differentiating children with current troublesome lung symptoms from those in the other groups (P < .001). AHR to methacholine separated children with current troublesome lung symptoms, early wheezing disorder, and bronchopulmonary dysplasia from the controls (P < .001), whereas the mannitol test did not distinguish among the study groups (P = .209). CONCLUSION: The methacholine and exercise challenge tests with IOS identify children with probable asthma characterized by troublesome lung symptoms and therefore may represent a practical aid in the evaluation of AHR in young children.

Very low birth weight and respiratory outcome: association between airway inflammation and hyperresponsiveness.

BACKGROUND: The respiratory outcomes after preterm birth have changed, and it is unclear whether increased airway hyperresponsiveness (AHR) later in childhood is associated with airway inflammation. OBJECTIVE: To investigate the association between AHR and fractional exhaled nitric oxide (FeNO), including the alveolar concentration of nitric oxide, in school-age children with very low birth weight (VLBW). METHODS: Twenty-nine children with VLBW, 33 children with a history of early wheeze, and 60 healthy controls underwent a FeNO measurement and bronchial challenge test with histamine. Atopy was assessed with skin prick tests. RESULTS: Children with VLBW had well-preserved baseline lung function but significantly increased AHR, expressed as the dose response slope (P < .001). Geometric mean FeNO levels were similar between VLBW children and healthy controls, and a history of bronchopulmonary dysplasia had no effect. In the VLBW and early wheeze groups, AHR was associated with FeNO (r = 0.47, P = .01, and r = 0.43, P = .013, respectively), but in a stratified analysis, this association was significant only in atopic individuals. By using the multiple flow FeNO technique, the bronchial nitric oxide flux rather than alveolar nitric oxide concentrations were associated with AHR in both children with early wheeze and VLBW. CONCLUSION: We conclude that in VLBW children AHR is related to FeNO but only in atopic individuals. Similar to children with early wheeze, this association is dependent on bronchial flux rather than alveolar nitric oxide concentration. It is likely that AHR is modified by atopic inflammation rather than by inflammatory process due to prematurity.

Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze.

BACKGROUND: Exposure to tobacco smoke is a well-known risk factor for childhood asthma and reduced lung function, but the effect on airway inflammation in preschool-aged children is unclear. OBJECTIVE: To examine the effect of parental smoking on lung function and fractional concentration of exhaled nitric oxide (Feno) in relation to both parental reports and children's urine cotinine concentrations in preschool-aged children with multiple-trigger wheeze. METHODS: A total of 105 3- to 7-year-old children with multiple-trigger wheeze and lung function abnormalities were recruited. Lung function was assessed by impulse oscillometry, and Feno measurements were performed. Exposure to tobacco smoke was determined by parental reports and measurement of children's urinary cotinine concentrations. RESULTS: Forty-three percent of the children were exposed to environmental tobacco smoke according to parental reports. The Feno level was significantly higher in children with a smoking mother (n = 27) than in children with a nonsmoking mother (23.4 vs 12.5 ppb, P = .006). The Feno level expressed as z score and the cotinine level correlated significantly (P = .03). Respiratory resistance at 5 Hz was higher in children exposed to maternal smoking than in others (0.99 vs 0.88 kPas/L, P = .005). Urinary cotinine concentrations reflected well parental reports on their daily smoking and increased relative to the number of cigarettes smoked in the family (P < .01). Atopy was found in 75% of the children, but it was not associated with the Feno value (P = .65). CONCLUSION: Maternal smoking was associated with increased Feno value and poorer lung function in steroid-naive preschool children with multiple-trigger wheeze. Larger controlled trials are needed to generalize the results.

Lung function, airway remodelling and inflammation in symptomatic infants: outcome at 3 years.

BACKGROUND: Relationships between early deficits of lung function, infant airway pathology and outcome in symptomatic infants are unclear. A study was undertaken to determine the associations between early lung function, airway histology and inflammation in symptomatic infants with the continuance of respiratory symptoms, lung function and subsequent use of inhaled asthma medication at the age of 3 years. METHODS: 53 children who underwent lung function measurements and bronchoscopy following referral to a specialist children's hospital for recurrent lower respiratory symptoms at a mean age of 1 year were followed up at 3 years of age. Assessments were made of respiratory symptoms during the previous year, lung function by oscillometry and atopy by skin prick testing. Individual data on the purchase of asthma medications were obtained from the Social Insurance Institution for the 12 months preceding the follow-up visit. RESULTS: 50 children (94%) were re-evaluated, of whom 40 had ongoing airway symptoms. 11/39 (28%) who underwent successful oscillometry had reduced lung function, 31/50 (62%) used inhaled corticosteroids (ICS) regularly and 12/50 (24%) used ICS intermittently. Abnormal lung function at infancy was associated with ongoing airway symptoms (p<0.001) and with the purchase of ICS (p=0.009) and ß agonists (p=0.002). Reticular basement membrane thickness in infancy and the numbers of mucosal mast cells, but not eosinophils, correlated significantly with the amount of ICS purchased at 3 years (p=0.003 and p=0.018, respectively). CONCLUSIONS: Reduced lung function, thickening of the reticular basement membrane and increased density of mucosal mast cells in infancy are associated with respiratory morbidity and treatment needs at age 3 years in this highly selected group of children.