Subsequent Wheezing Research Articles

Infant Respiratory Tract Infections or Wheeze and Maternal Vitamin D in Pregnancy: A Systematic Review.

Respiratory tract infections (RTIs) are a common cause of morbidity and mortality in young children and can be associated with wheeze. Vitamin D can have a protective role against RTI. A systematic search of PubMed, Embase and the Cochrane library was performed. Titles and abstracts were evaluated, and selected articles were reviewed by 2 authors. We included randomized controlled trials (RCTs) investigating the effect of vitamin D supplementation during pregnancy on RTIs or wheeze in children of 5 years of age or younger. Observational studies on the association between serum 25-hydroxyvitamin D during pregnancy, or at birth, and RTIs and/or wheeze were included. The protocol was registered on PROSPERO (Registration number: CRD42015019183). Of 4 RCTs, 1 showed a protective effect of a high daily dose (2000 IU) of vitamin D during pregnancy on offspring RTI doctor visits (P = 0.004; the RCT also included 800 IU/d supplement to the infants until 6 months). Meta-analysis of 3 RCTs showed a reduced relative risk for offspring wheeze when mothers were supplemented with vitamin D during pregnancy [relative risk: 0.81 (95% confidence interval: 0.68-0.97), P = 0.025]. In 3 of 4 strong-quality, and 5 of 10 moderate-quality observational studies, an inverse association between pregnancy and cord 25-hydroxyvitamin D and subsequent wheeze and/or RTI was seen. Growing evidence supports a preventive role of vitamin D during pregnancy on offspring wheeze and/or RTI. Recommendations in future intervention studies may need to exceed current recommendations of vitamin D supplementation during pregnancy to show benefit against childhood wheeze or infections.

Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial

Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial. We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25-hydroxyvitamin D3 (25[OH]D) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring. The Vitamin D Antenatal Asthma Reduction Trial is a randomized trial of pregnant women at risk of having children with asthma randomized to 4400international units/d vitamin D or placebo plus 400international units/d vitamin D. Asthma and recurrent wheezing until age 3years were recorded. African American (AA) women (n=312) had lower initial levels of 25(OH)D (mean [SD], 17.6ng/mL [8.3ng/mL]) compared with non-AA women (n=400; 27.1ng/mL [9.7ng/mL], P<.001). No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring (P for interaction=.77). Having an initial level of greater than 30ng/mL and being randomized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3years compared with having an initial level of less than 20ng/mL and receiving placebo (adjusted odds ratio, 0.42; 95% CI, 0.19-0.91). We did not find differences between AA and non-AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3years. Maternal supplementation of vitamin D, particularly in mothers with initial 25(OH)D levels of greater than 30ng/mL, reduced asthma/recurrent wheeze in the offspring through age 3years, suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheezeprevention in early life.

Azithromycin therapy during respiratory syncytial virus bronchiolitis: Upper airway microbiome alterations and subsequent recurrent wheeze

Azithromycin therapy during respiratory syncytial virus bronchiolitis: Upper airway microbiome alterations and subsequent recurrent wheeze

Viral Load in Infants Hospitalized for Respiratory Syncytial Virus Bronchiolitis Correlates with Recurrent Wheezing at Thirty-Six-Month Follow-Up.

The relationship between viral infection, host immune response in infants with respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing is discussed. We measured RSV-RNA load and interferon-λ1-3 expression in the nasopharyngeal washings from 68 infants hospitalized for RSV bronchiolitis, and wheezing was assessed 36 months after the first episode of bronchiolitis. Higher RSV-RNA load and higher interferon-λ2/3 levels were found in children with recurrent wheezing at 36-month follow-up.

Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy

Background: Infants with lower respiratory tract infections (LRTIs) are at an increased risk of developing childhood wheezing illnesses (including asthma), but it is not currently possible to predict those at risk for these long-term outcomes. The current objective was to examine whether urine levels of club cell 16-kDa secretory protein (CC16) at the time of an infant LRTI are associated with the development of childhood wheezing illnesses. Methods: Prospective study of 133 previously healthy infants enrolled during a healthcare visit for a LRTI and followed longitudinally for childhood wheezing illnesses. Urine levels of CC16 at the time of enrollment were measured after validating a commercially available enzyme-linked immunosorbent assay kit for serum. The outcome of interest was parental report of subsequent childhood wheeze (defined as ≥1 episode of wheezing following the initial LRTI) at the 1-year follow-up visit. Logistic regression was used for the main analysis. Results: The median (interquartile range) urine levels of CC16 (ng/mg of creatinine) at the time of an infant LRTI were 11.1 (7.7-20.1) for infants with subsequent childhood wheeze and 13.4 (8.3-61.1) for those without (p = 0.11). In the main multivariate analysis using a logarithmic transformation of the urine levels of CC16, a twofold increase in urine levels of CC16 was associated with ∼30% decreased odds (OR = 0.74 [95% confidence interval (CI) 0.56-0.98], p = 0.04) of subsequent childhood wheeze after adjustment for potential confounders. Conclusions: An inverse association was found between urine levels of CC16 at the time of an infant LRTI and the odds of subsequent childhood wheeze. Urine CC16 may be a useful biomarker of the development of childhood wheezing illnesses after LRTIs in infancy.

The Role of Human Milk Immunomodulators in Protecting Against Viral Bronchiolitis and Development of Chronic Wheezing Illness.

Infants who are breastfed are at an immunological advantage when compared with formula fed infants, evidenced by decreased incidence of infections and diminished propensity for long term conditions, including chronic wheeze and/or asthma. Exclusive breastfeeding reduces the duration of hospital admission, risk of respiratory failure and requirement for supplemental oxygen in infants hospitalised with bronchiolitis suggesting a potentially protective mechanism. This review examines the evidence and potential pathways for protection by immunomodulatory factors in human milk against the most common viral cause of bronchiolitis, respiratory syncytial virus (RSV), and subsequent recurrent wheeze in infants. Further investigations into the interplay between respiratory virus infections such as RSV and how they affect, and are affected by, human milk immunomodulators is necessary if we are to gain a true understanding of how breastfeeding protects many infants but not all against infections, and how this relates to long-term protection against conditions such as chronic wheezing illness or asthma.

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms. The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data. In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child. Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

Clarifying Costs and Benefits of Respiratory Syncytial Virus Immunoprophylaxis

In response to recent studies demonstrating that palivizumab use in moderate preterm infants may decrease subsequent wheezing, Meissner and Kimberlin1 discuss costs associated with palivizumab but make multiple statements that may not be consistent with the best available evidence.The stated hospitalization cost of $8530 (2009$) is not representative of respiratory syncytial virus (RSV) hospitalizations among palivizumab-eligible infants; it is the average cost of bronchiolitis hospitalizations among US children <2 years.2 Using the same source, the Kids’ Inpatient Database, the average RSV hospitalization (International Classification of Diseases, Ninth Revision, Clinical Modification 079.6, 466.11, 480.1) cost for all infants was $14 832 (2009$). Among high-risk infants, costs of RSV hospitalization and associated care through 12 months of age range from $20 160 to $39 399 (2010$).3The authors also state the number needed to treat (NNT) with palivizumab to prevent 1 RSV hospitalization for most infants ranges from 19 to 170. In the Canadian Pediatric Society’s RSV prevention position statement, high-quality NNT estimates range from 12 to 23 depending on the population. Lower quality estimates from studies of health care utilization databases, such as those referenced by the authors, often yield higher NNTs due to underdiagnosis of RSV and limited use of RSV-specific codes.Meissner and Kimberlin1 state that RSV hospitalizations are becoming less common among children eligible for palivizumab, citing a 17% decrease in bronchiolitis hospitalization rates from 2000 to 2009 among US children <2 years.2 However, Hasegawa et al2 also found a 34% increase in children with high-risk conditions from 2000 to 2009. According to a personal communication with Dr Hasegawa, the hospitalization rate among children at high risk rose by 29%. This increase despite palivizumab use is not surprising given that most children at high risk do not receive palivizumab and use has declined since 2006.Concerning the cost of palivizumab, the authors state that rebates may modify the cost, but the cost presented does not incorporate rebates. Federally mandated rebates for Medicaid recipients and discounts for 340B-eligible organizations have resulted in ∼40% reduction in palivizumab cost for ∼60% of palivizumab recipients, as described in a recent publication3 and a Centers for Disease Control and Prevention analysis at the June 23, 2010, Advisory Committee on Immunization Practices.Finally, the authors state that mortality reduction cannot be included in palivizumab analyses because it has not been demonstrated in randomized trials. However, mortality reductions are commonly included in cost-effectiveness studies even without statistically significant differences in randomized trials. Two examples include an economic evaluation of pediatric influenza vaccination conducted by the Centers for Disease Control and Prevention and investigators from Harvard University, as well as the UK Health Technology Assessment of palivizumab.4 There is no evidence to support the authors’ statement that “adverse long-term outcomes such as death are not prevented by passive immunotherapy.”Cost-effectiveness analyses of palivizumab should consider all downstream costs and savings and use the best available evidence. As the authors state, quality of life and other factors must be considered. Calculating cost per quality-adjusted life-year gained is the recommended approach to understand the benefits of an intervention relative to costs and enables comparison with other health interventions.5

Clinical analysis and follow-up of neonatal lower respiratory tract infection with respiratory syncytial virus

Objective To investigate the clinical features of neonatal lower respiratory tract infection (LRTI) with respiratory syncytial virus(RSV), and to explore the relationship between clinical features and recurrent cough or wheezing after discharge. Methods From May 2008 to May 2013, the data of 41 neonates diagnosed as LRTI with RSV infection in New Century International Children's Hospital were analyzed retrospectively.The clinical features and follow-up results were observed. Results All the neonates had cough, 92.7% (38/41 cases) had choking, 85.4% (35/41 cases) had runny nose and nasal obstruction, 31.7% (13/41 cases) had fever, 65.9%(27/41 cases) had whee-zing sound during physical examination, 29.3%(12/41 cases)of the neonates were accompanied with bacterial infection(n=29), in which 50.0% (6/12 cases) were infected by staphylococcus aureus.Compared to the neonates only with RSV infection, the proportion of fever was higher in those with RSV combined with bacterial infection(n=12) (χ2=6.034, P<0.05), and there were no statistical differences between the neonates with or without bacterial infection in white blood cell count and with or without shadow in chest X-ray(χ2 =0.859, 2.064, P=0.485, 0.202). Compared with the neonates without family history of atopy, the neonates with the family history of atopy were more likely to get wheezing (88.2%vs 57.1%, χ2=4.871, P<0.05)during primary infection.During the follow-up, there was higher proportion of children with family history of atopy in the group with subsequent recurrent cough and/or wheezing than in the group without subsequent recurrent cough and/or wheezing(71.4% vs 26.3%, χ2=6.388, P<0.05). Conclusions Cough, choking are most common symptoms in neonatal LRTI with RSV, and there is no wheezing sound during phy-sical examination in some neonates.LRTI with RSV is likely combined with bacterial infection.Wheezing is more common in the neonates with family history of atopy.The RSV LTRI neonates with family history of atopy incline to get subsequent recurrent cough or wheeze after discharge. Key words: Respiratory syncytial virus; Lower respiratory tract infection; Follow-up; Family history of atopy; Recurrent cough or wheeze; Infant, newborn

Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years

Most wheezing episodes in infants are caused and exacerbated by virus-induced lower respiratory tract infections. However, there are few reports of epidemiologic and clinical virus-specific research with a focus on virus-induced wheezing. The purpose of the current study was to characterize the clinical presentation of virus-induced wheezing in pediatric patients <3years of age who were hospitalized with lower respiratory tract infections. Of the 412 patients in the study, 216 were followed for 3years. Nasopharyngeal aspirates collected from the patients at the time of admission were examined for the presence of respiratory syncytial virus (RSV), rhinovirus (RV), parainfluenza-3 virus (PIV-3), human metapneumovirus (hMPV), and influenza virus (Flu) using reverse-transcription polymerase chain reaction and rapid diagnostic tests. Clinical signs were assessed using a severity scoring system. In patients with wheezing at the time of admission, RSV, RV, RSV+RV, Flu, PIV-3, and hMPV were detected in 33, 14, 8, 8, 5, and 3% of samples, respectively. There were no differences in age and severity scores between patients harboring more prevalent viruses (RSV and RV) and those with less common infections. Patients with wheezing and RV-positive aspirates at the time of admission were more likely to develop subsequent wheezing during the following 3years. RSV and RV infections are factors in the development and exacerbation of wheezing after virus-induced lower respiratory tract infections. Moreover, RV-induced wheezing may be associated with subsequent recurrent wheezing and the development of asthma.

Association between body composition and subsequent childhood asthma and wheeze outcomes in the Southampton Women's Survey cohort study

BackgroundObesity is associated with adult asthma, notably non-atopic asthma. The association between obesity and childhood asthma is unclear and complicated by changes in body composition during growth. We aimed to determine whether and how body composition and change in body composition are associated with childhood asthma, wheeze, and atopic outcomes. MethodsParticipants were 940 children born between February, 2000, and June, 2003, to women recruited within the Southampton Women's Survey. Body composition was characterised with body-mass index (BMI) at 3 years and 6 years of age, standardised for age and sex; lean and fat mass measured at 4 years and 6 years of age with dual energy X-ray absorptiometry (DEXA) scanning; and serial measures of subscapular skinfold thickness. Relative risks were calculated with Poisson regression for questionnaire-determined asthma and wheeze at age 6 years. Wheeze was defined as atopic or non-atopic according to skin prick testing. Spirometry, bronchial hyper-responsiveness (BHR), and fractional exhaled nitric oxide (FeNO) were assessed at 6 years of age. Potential maternal and socioeconomic confounders were adjusted for and exposure variables combined in multivariable models. Written informed parental consent was obtained for each participant. The study was approved by the Southampton and South West Hampshire Local Research Ethics Committee. FindingsBMI at 6 years of age was not associated with asthma, atopy, any wheeze phenotype, or measure of lung function. Higher BMI at age 3 years was associated with greater BHR at age 6 (p=0·032) and with lower forced expiratory volume in the first second of expiration corrected for lung size by dividing by forced vital capacity (FEV1/FVC) (p=0·013). Although a conditional increase in subscapular skinfold thickness between 1 and 2 years was associated with asthma at age 6 years (relative risk 1·27, 95% CI 1·07–1·51), a decrease in subscapular skinfold thickness between 2 and 3 years was associated with increased risks of asthma (0·73, 0·55–0·96), wheeze, atopy, and atopic wheeze at age 6 years and with greater FeNO. InterpretationCurrent BMI at 6 years was not associated with asthma symptoms or impaired lung function in this cohort of children at age 6 years, although a higher BMI at age 3 years was associated with increased BHR and reduced FEV1/FVC at age 6 years. More rapid adiposity gain between ages 1 and 2 years was associated with increased asthma risk; although this finding might be an adverse effect of increased adiposity on respiratory development, rapid postnatal adiposity gain might be catch-up growth and might be a marker for adverse in-utero factors. By contrast, lower adiposity gain between 2 and 3 years was associated with asthma and markers of atopy and eosinophilic airway inflammation, suggesting that factors associated with poor weight gain in this period, such as recurrent respiratory infection, might predispose to atopic sensitisation. FundingMedical Research Council, British Heart Foundation, Food Standards Agency, Arthritis Research UK, National Osteoporosis Society, International Osteoporosis Foundation, Cohen Trust, NIHR Southampton Biomedical Research Centre, NIHR Oxford Biomedical Research Unit, British Lung Foundation.

Lack of Long-term Effects of High-dose Inhaled Beclomethasone for Respiratory Syncytial Virus Bronchiolitis

Previously, we showed that high-dose early initiated inhaled corticosteroids during respiratory syncytial virus bronchiolitis partially and transiently prevents subsequent recurrent wheeze. Here, we study treatment effect on lung function at age 6. This is a 6-year follow-up report of a randomized placebo-controlled trial, in which 185 infants hospitalized for respiratory syncytial virus bronchiolitis were treated with early initiated, high-dose inhaled beclomethasone (n = 86) or placebo (n = 99) for 3 months. The primary outcome was forced expiratory volume in 1 second as percentage predicted. Secondary outcomes were bronchial hyperresponsiveness, physician-diagnosed asthma, hay fever and eczema. Possible toxicity was assessed by linear growth measurements. At age 6, no significant differences were found in mean forced expiratory volume in 1 second percentage predicted between beclomethasone-treated and placebo-treated patients (91.4 vs. 93.4, mean difference 2.05 (95% confidence interval: -1.98 to 6.08). The proportion of bronchial hyperresponsiveness, physician-diagnosed asthma, parent reported hay fever and eczema was comparable between groups. There were no differences in linear growth. Early initiated prolonged treatment with high-dose inhaled beclomethasone during hospitalization for respiratory syncytial virus infection during infancy did not improve the long-term respiratory outcome, but was safe.

Effect of Palivizumab Prophylaxis on Subsequent Recurrent Wheezing in Preterm Infants

Palivizumab effectively prevents severe respiratory syncytial virus (RSV) disease in preterm infants. Our objective was to test whether palivizumab prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing up to 3 years of life. We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 3 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice. In April 2008, 52 hospitals were recruited. Study participants were prospectively followed to the age of 3 years. Parents of study subjects reported the infants' physician's assessment of recurrent wheezing, used a report card and a novel mobile phone-based reporting system by using the Internet. The primary end point was the incidence of physician-diagnosed recurrent wheezing. Of 444 preterm infants enrolled, 349 received palivizumab during the first 6 months of life and 95 infants did not. Physician-diagnosed recurrent wheezing was observed in 6.4% and 18.9% of infants in the treated and untreated groups, respectively (P < .001). This difference remained significant after adjustment for known risk factors of recurrent wheezing (P < .001). Palivizumab prophylaxis administered to preterm infants 33 to 35 weeks' gestational age is associated with a significantly lower incidence of recurrent wheezing during the first 3 years of life.

Effect of Palivizumab Prophylaxis on Subsequent Recurrent Wheezing in Preterm Infants

Effect of Palivizumab Prophylaxis on Subsequent Recurrent Wheezing in Preterm Infants

Progress in Understanding the Link Between RSV Infection and Recurrent Wheezing

Severe respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent wheezing and childhood asthma, but the pathogenesis is poorly

Respiratory Syncytial Virus and Recurrent Wheeze in Healthy Preterm Infants

BackgroundRespiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants.MethodsIn the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis.ResultsPalivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group [1.8%] vs. 2309 of 51,726 days [4.5%] in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01).ConclusionsIn otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.)

The role of early life viral bronchiolitis in the inception of asthma

PROPOSE OF REVIEW: Cumulative evidence suggest that early life bronchiolitis is a major risk factor for subsequent wheezing episodes and asthma. The purpose of this review is to present the recent findings and current perspectives regarding the interplay between bronchiolitis and long-term respiratory outcomes. Recent studies have supported the long-recognized link between early life severe respiratory syncytial virus bronchiolitis and the physician diagnosis of asthma by school age, and this association appears to continue into early adulthood. Evidence is accumulating regarding the role of early life infection with human rhinovirus as an important antecedent for future asthma. Whether viral bronchiolitis is causal or an early manifestation of future asthma remains uncertain. Vitamin D status has emerged as a potential modifying factor for viral-induced wheeze and could potentially influence the development of asthma. Viral bronchiolitis early in life is a major and potential long-term risk factor for subsequent wheezing and asthma. Whether the association between bronchiolitis and subsequent asthma is due to causality or a reflection of predisposition may be dependent on host factors and virus-specific effects.

Cellular and humoral immunity of virus-induced asthma

Asthma inception is associated with respiratory viral infection, especially infection with respiratory syncytial virus (RSV) and/or human rhinovirus (HRV), in the vast majority of cases. However, the reason why RSV and HRV induce the majority of bronchiolitis cases during early childhood and why only a small percentage of children with RSV- and HRV-induced bronchiolitis later develop asthma remains unclear. A genetic association study has revealed the important interaction between viral illness and genetic variants in patients with asthma. Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV. RSV and HRV infections in infants with deficient innate immune response and the dysfunction of regulatory T cells are considered to be a risk factor for the development of asthma. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses, but the converse is not true. Some evidence of virus specificity exists, in that allergic sensitization specifically increased the risk of wheezing in individuals infected with HRV, but not RSV. Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing. However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy. These findings suggest that infection with RSV and infection with HRV might predispose individuals to recurrent wheezing through an atopy-independent and an atopy-dependent mechanism, respectively. Respiratory virus-induced wheezing illnesses may encompass multiple sub-phenotypes that relate to asthma in different ways.

Respiratory syncytial virus infection and chronic respiratory morbidity – is there a functional or genetic predisposition?

A systematic literature review has been undertaken. Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infancy is associated with chronic respiratory morbidity. Premorbid abnormal lung function may predispose to RVS LRTI in prematurely born infants. Single-nucleotide polymorphisms in genes coding for IL-8, IL-19, IL-20, IL-13 mannose-binding lectin, IFNG and a RANTES polymorphism have been associated with subsequent wheeze following RSV LRTI in term-born infants.

Exhaled Nitric Oxide in Acute Phase of Bronchiolitis and Its Relation with Episodes of Subsequent Wheezing in Children of Preschool Age

BACKGROUND: Fractional exhaled nitric oxide (FENO) levels are increased in children with asthma and in infants with recurrent wheezing, but the role of FENO in the acute phase of bronchiolitis is still not defined. OBJECTIVE: The aim of this study is to evaluate FENO values in the acute phase of bronchiolitis, compare them with healthy infants, and relate those values with the appearance of other wheezing episodes. METHODS: FENO values were determined in infants between 2 months and 2 years affected with RVS bronchiolitis by offline method. The FENO values collected in the acute phase were related with the respiratory clinical symptoms presented in the 2 years following the episode. RESULTS: A total of 30 patients were recruited: 15 in the bronchiolitis group and 15 in the control group. The average of the FENO values in the acute phase was 18.74 ppb (range 2-88) in the bronchiolitis group, and 8.75 ppb (range 2-24) in the control group. However, these results showed no significant statistical differences (p=0.176). Nevertheless, we found a positive correlation between the FENO values and the clinical score (Downes) of the bronchiolitis episode (p=0.023). In infants that presented other wheezing episodes in the 2 years after, the average of FENO in the acute phase of the first episode was 23.1 ppb (average of 10.25 ppb) versus 8.4 ppb (average 5.4 ppb) in the group of patients with no other episodes. The comparison of averages has no statistical significance. CONCLUSION: We found no differences in FENO between infants with bronchiolitis and healthy ones. The FENO values in the acute phase seems to be related to the severity of the disease but do not predict the appearance of wheezing episodes in the following 2 years.