Search

Background No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. Methods We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. Results Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P

Allergic diseases exclusively affect tissues that face environmental challenges and harbor endogenous bacterial microbiota. The microbes inhabiting the affected tissues may not be mere bystanders in this process but actively affect the risk of allergic sensitization, disease development, and exacerbation or abatement of symptoms. Experimental evidence provides several plausible means by which the human microbiota could influence the development of allergic diseases including, but not limited to, effects on antigen presentation and induction of tolerance and allergen permeation by endorsing or disrupting epithelial barrier integrity. Epidemiological evidence attests to the significance of age-appropriate, nonpathogenic microbiota development in skin, gastrointestinal tract, and airways for protection against allergic disease development. Thus, there exist potential targets for preventive actions either in the prenatal or postnatal period. These could include maternal dietary interventions, antibiotic stewardship for both the mother and infant, reducing elective cesarean deliveries, and understanding barriers to breastfeeding and timing of food diversification. In here, we will review the current understanding and evidence of allergy-associated human microbiota patterns, their role in the development of allergic diseases, and how we could harness these associations to our benefit against allergies.

BACKGROUND: Low airway surface pH is associated with many airway diseases, impairs antimicrobial host defense, and worsens airway inflammation. Inhaled Optate is designed to safely raise airway surface pH and is well tolerated in humans. Raising intracellular pH partially prevents activation of SARS-CoV-2 in primary normal human airway epithelial (NHAE) cells, decreasing viral replication by several mechanisms. METHODS: We grew primary NHAE cells from healthy subjects, infected them with SARS-CoV-2 (isolate USA-WA1/2020), and used clinical Optate at concentrations used in humans in vivo to determine whether Optate would prevent viral infection and replication. Cells were pretreated with Optate or placebo prior to infection (multiplicity of infection = 1), and viral replication was determined with plaque assay and nucleocapsid (N) protein levels. Healthy human subjects also inhaled Optate as part of a Phase 2a safety trial. RESULTS: Optate almost completely prevented viral replication at each time point between 24 h and 120 h, relative to placebo, on both plaque assay and N protein expression (P < .001). Mechanistically, Optate inhibited expression of major endosomal trafficking genes and raised NHAE intracellular pH. Optate had no effect on NHAE cell viability at any time point. Inhaled Optate was well tolerated in 10 normal subjects, with no change in lung function, vital signs, or oxygenation. CONCLUSIONS: Inhaled Optate may be well suited for a clinical trial in patients with pulmonary SARS-CoV-2 infection. However, it is vitally important for patient safety that formulations designed for inhalation with regard to pH, isotonicity, and osmolality be used. An inhalational treatment that safely prevents SARS-CoV-2 viral replication could be helpful for treating patients with pulmonary SARS-CoV-2 infection.

Food allergy is a growing health and safety concern that affects up to 8% of school-age children. Because children spend a significant part of their day in school, and the overall number of school-age children with food allergy has been increasing, management of food allergies relies on the collaboration of allergists, families, and schools to treat and prevent acute allergic reactions. For schools, this involves policies centered on food allergen avoidance, preparedness with epinephrine autoinjectors, adequate school personnel training, and accommodations for an equal opportunity learning environment. Partnerships with allergists, primary care providers, students, families, school nurses, and school staff are vital for creating individualized and effective care plans that will allow all children, including those with food allergies, a safe and nurturing learning environment.

Over the past decade, there have been substantial advances in our understanding about how viral infections regulate asthma. Important lessons have been learned from birth cohort studies examining viral infections and subsequent asthma and from understanding the relationships between host genetics and viral infections, the contributions of respiratory viral infections to patterns of immune development, the impact of environmental exposure on the severity of viral infections, and how the viral genome influences host immune responses to viral infections. Further, there has been major progress in our knowledge about how bacteria regulate host immune responses in asthma pathogenesis. In this article, we also examine the dynamics of bacterial colonization of the respiratory tract during viral upper respiratory tract infection, in addition to the relationship of the gut and respiratory microbiomes with respiratory viral infections. Finally, we focus on potential interventions that could decrease virus-induced wheezing and asthma. There are emerging therapeutic options to decrease the severity of wheezing exacerbations caused by respiratory viral infections. Primary prevention is a major goal, and a strategy toward this end is considered.

The lung microbiome is associated with host immune response and health outcomes in experimental models and patient cohorts. Lung microbiome research is increasing in volume and scope; however, there are no established guidelines for study design, conduct and reporting of lung microbiome studies. Standardized approaches to yield reliable and reproducible data that can be synthesized across studies, will ultimately improve the scientific rigor and impact of published work and greatly benefit microbiome research. In this review, we identify and address several key elements of microbiome research: conceptual modeling and hypothesis framing, study design, experimental methodology and pitfalls, data analysis and reporting considerations. Finally, we explore possible future directions and research opportunities. Our goal is to aid investigators who are interested in this burgeoning research area and will hopefully provide the foundation for formulating consensus approaches in lung microbiome research.

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. Acurrent challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma.

Background: Asthma is a chronic respiratory disease that affects 10% of children. Infant wheeze at 1 year and the subsequent development of asthma in early childhood has been associated with infant gut dysbiosis. However, little is known about the relationship between neonatal gut microbiome and the development of wheeze during the first 18 months of life. We hypothesize that the gut microbiome at birth and throughout the first 18 months of life is associated with infant wheeze. Project Methods: Stool samples were collected from infants at birth, 1, 3, and 12 months of age. The Illumina Miseq system was used to sequence the bacterial V4 region of 16S-rRNA gene. Mothur software was used for analysis. Statistical analysis was used to measure stool shannon diversity and evenness as they relate to timepoint and wheeze vs no wheeze groups. Results: The study population consisted of 28 infants (18 males and 10 females). 11% of participants reported they had been diagnosed with wheeze by a physician (n=3). Statistical analysis of shannon diversity showed no differences in the stool between participants who wheeze vs those who do not wheeze (p=0.78). No difference in stool evenness was detected between participants who reported wheeze vs no wheeze (p=0.71). However, this analysis includes multiple timepoints. Analysis of stool shannon diversity across timepoints did show a significant difference in stool microbiome (p=0.01). Conclusion: No differences in stool microbiome were found between infants who do not wheeze and those who do. Further studies can investigate a greater number of samples at each timepoint and relate these to objective measures such as pulmonary function tests. Understanding the association between infant gut dysbiosis and wheeze could have implications for predicting development of asthma in early childhood and potentially lead to targeted interventions.

Allergies are a result of allergen proteins cross-linking allergen-specific IgE (sIgE) on the surface of mast cells and basophils. The diversity and complexity of allergen epitopes, and high-affinity of the sIgE-allergen interaction have impaired the development of allergen-specific inhibitors of allergic responses. This study presents a design of food allergen-specific sIgE inhibitors named covalent heterobivalent inhibitors (cHBIs) that selectively form covalent bonds to only sIgEs, thereby permanently inhibiting them. Using screening reagents termed nanoallergens, we identified two immunodominant epitopes in peanuts that were common in a population of 16 allergic patients. Two cHBIs designed to inhibit only these two epitopes completely abrogated the allergic response in 14 of the 16 patients in an in vitro assay and inhibited basophil activation in an allergic patient ex vivo analysis. The efficacy of the cHBI design has valuable clinical implications for many allergen-specific responses and more broadly for any antibody-based disease.

Background Recent studies have suggested that removing foods from the diet to manage atopic dermatitis (AD), based on positive allergy test results, may lead to immediate allergic reactions on reintroduction of that food. Objective To examine the frequency of oral food challenge (OFC) failures among foods removed from the diet as suspected AD triggers, focusing on the 5 major food allergens in the United States. Methods OFCs to egg, milk, peanut, soy, and wheat, performed from 2008 to 2014, at a children's hospital's allergy clinics, were reviewed. OFCs were offered based on history and laboratory values. Reasons for food avoidance were classified as food allergy (IgE-mediated reaction occurring within 2 hours); sensitization only (lack of introduction because of positive test results); and removal because of test results during AD evaluation. Results There were 442 OFCs performed, with 89 failures (20.1%). Reasons for OFCs included a history of food allergy (320 of 442 [72.4%]), food sensitization without any introduction (77 of 442 [17.4%]), and AD (45 of 442 [10.2%]). OFC failures among those who had food allergy (70 of 320 [21.9%]), sensitization only (13 of 77 [16.9%]), and suspected AD trigger (6 of 45 [13.3%]) did not significantly differ (P = .63). Wheat was more likely to be avoided than the other 4 foods for AD concerns (P Conclusion The frequency of OFC failure among those who removed foods suspected as AD triggers was 13.3%, indicating a loss of tolerance. Restriction of foods to manage AD must be done with caution and close monitoring.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.

PURPOSE OF REVIEW: Evidence suggests that the microbiome of the skin, gastrointestinal tract and airway contribute to health and disease. As we learn more about the role that the microbiota plays in allergic disease development, we can develop therapeutics to alter this pathway. RECENT FINDINGS: Epidemiologic studies reveal that an association exists between environmental exposures which alter the microbiota, and developing atopic dermatitis, food allergy and/or asthma. In fact, samples from the skin, gastrointestinal tract and respiratory tract, reveal distinct microbiotas compared to healthy controls, with microbial changes (dysbiosis) often preceding the development of allergic disease. Mechanistic studies have confirmed that microbes can either promote skin, gut and airway health by strengthening barrier integrity, or they can alter skin integrity and damage gut and airway epithelium. SUMMARY: In this review, we will discuss recent studies that reveal the link between the microbiota and immune development, and we will discuss ways to influence these changes.

Rationale Sputum and bronchoalveolar lavage fluid (BALF) are often obtained to elucidate the lower airway microbiota in adults. Acquiring sputum samples from children is difficult and obtaining samples via bronchoscopy in children proves challenging due to the need for anesthesia and specialized procedural expertise; therefore nasopharyngeal (NP) swabs are often used as surrogates when investigating the pediatric airway microbiota. In adults, the airway microbiota differs significantly between NP and BALF samples however, minimal data exist in children. Objectives To compare NP and BALF samples in children undergoing clinically indicated bronchoscopy. Methods NP and BALF samples were collected during clinically indicated bronchoscopy. Bacterial DNA was extracted from 72 samples (36 NP/BALF pairs); the bacterial V1-V3 region of the 16S rRNA gene was amplified and sequenced on the Illumina Miseq platform. Analysis was performed using mothur software. Results Compared to NP samples, BALF had increased richness and diversity. Similarity between paired NP and BALF (intra-subject) samples was greater than inter-subject samples (P = 0.0006). NP samples contained more Actinobacteria (2.2% vs 21%; adjusted P = 1.4 × 10-6 ), while BALF contained more Bacteroidetes (29.5% vs 3.2%; adjusted P = 1.2 × 10-9 ). At the genus level several differences existed, however Streptococcus abundance was similar in both sample types (NP 37.3% vs BAL 36.1%; adjusted P = 0.8). Conclusion Our results provide evidence that NP samples can be used to distinguish differences between children, but the relative abundance of organisms may differ between the nasopharynx and lower airway in pediatric patients. Studies utilizing NP samples as surrogates for the lower airway should be interpreted with caution.

A Bedard, K Northstone, AJ Henderson, S O Shaheen. Eur Respir J. 2020;55(3):1901215 To assess whether adherence to a Mediterranean diet in pregnancy was associated with a reduced risk of asthma and other atopic outcomes and a higher lung function test in school-aged offspring. The study used a population birth cohort out of Avon, United Kingdom that included 14 541 white pregnant women. Women had a delivery date between April 1, 1991, and December 31, 1992. Out of this cohort, 8907 mother-child pairs were analyzed to include only women of singleton or twin deliveries, with information on their diet during pregnancy and at least one of the outcomes of interest in their offspring. Data on maternal diet were …

C Baggott, HK Reddel, J Hardy. Eur Respir J. 2020;55(4):1902073 Symptom-driven low-dose inhaled corticosteroid–formoterol use is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma (GINA). However, there are no data on patient preferences for this regimen. The purpose of this study was to investigate patient preferences between two regimens: symptom-driven budesonide-formoterol versus maintenance inhaled corticosteroid (ICS) with a separate as-needed reliever inhaler. This study …

K Dos Santos, CJ Lodge, MJ Abramson. Chest. 2020;157(2):334–341 To examine the association between early-life exposure to antibiotics and lung function and to assess whether antibiotic use puts children with mutations of the glutathione S-transferase (GST) superfamily at greater risk of developing lung function impairment. This study included 620 infants with a family history of allergy from the Melbourne Atopy Cohort Study in Australia. This study collected parent-reported data via …

We read the article “Virus–virus interactions impact the population dynamics of influenza and the common cold” by Nickbakhsh et al. (1) with great interest. The authors analyzed a large Scottish dataset consisting of virology results from patients with acute respiratory illnesses and used mathematical models to identify a negative interaction between influenza and rhinovirus (RV) infection. Furthermore, they performed epidemiologic simulations demonstrating that influenza-mediated induction of a refractory period could account for the significant reduction in RV illness prevalence. In fact, we demonstrated that influenza can induce a refractory period using individual-level data obtained from a cohort of children that … [↵][1]1To whom correspondence may be addressed. Email: kloepfer{at}iu.edu. [1]: #xref-corresp-1-1

Background and Hypothesis: Early wheezing and persistent cough in young children can be a first indication of asthma. Studies show that infants later diagnosed with asthma commonly exhibit airway microbiome dysbiosis particularly with pathogenic bacteria. Two such bacteria, Moraxella catarrhalis and Haemophilus influenzae, can stimulate pro-inflammatory cytokines such as IL-5. Because IL-5 can signal eosinophil production, we hypothesize children with asthma and positive bronchoalveolar lavage fluid (BALF) culture will have elevated BALF eosinophils. Project Methods: Children undergoing clinically indicated bronchoscopy in the Riley Hospital outpatient center were recruited. Chart review was conducted to examine associations between BALF culture, BALF differential cytology, diagnoses, antibiotic history, and demographic data from biobank participants. Exclusion criteria included: diagnosis of cystic fibrosis or pulmonary ciliary dyskinesia; BALF culture not performed; and/or hypocellular sample. Statistical analyses included Student’s t-test, Wilcoxon rank-sum tests, and Chi-Square tests (verified with Fisher’s Exact tests). Results: 94 samples were analyzed (37% female, age: 1mos – 17 yrs). BALF was positive for the following bacteria: M. catarrhalis (26%), H. influenzae (28%), S. pneumoniae (27%), and S. aureus (17%). Haemophilus in BALF was associated with elevated eosinophils (p = .03) and neutrophils (p = .04) and decreased macrophages (p = .001). Asthma diagnosis and prior antibiotic use were not significantly associated with positive BALF culture. Conclusion and Potential Impact: Haemophilus was associated with elevated eosinophils in the airway. The impact of this observation remains unclear. Further research is necessary to determine pathways that lead to these observed changes within the airway.

A Bedard, K Northstone, JW Holloway, AJ Henderson, SO Shaheen. Eur Respir J. 2018;52(2):1800507 To investigate the associations between maternal intake of dietary antioxidants in pregnancy and childhood respiratory and atopic outcomes (including lung function) and to explore whether these associations were modified by maternal smoking during pregnancy and common maternal antioxidant gene polymorphisms. The study was focused on 8915 mother-child pairs who participated in a population-based birth cohort in Avon, United Kingdom. Researchers …

EB Milanzi, GH Koppelman, HA Smit. Eur Respir J. 2018;52(3):1800218 Evidence for the effects of air pollution exposure on lung function growth into adolescence is scarce. Therefore, the purpose of this study was to investigate the associations of air pollution exposure from birth with lung function growth from ages 8 to 16 and lung function at age 16. Potential confounders (sex and asthma diagnosis) were also explored. The study was performed within the Dutch population-based Prevention and …

Objective To confirm new observations on peanut allergy and answer current concerns that families and healthcare providers have about peanut allergy. Study design Children who presented with a story of peanut allergy or peanut sensitization were asked to participate in a registry, which allowed an analysis focused on questions that a food allergy support group had about children with peanut allergy or sensitization. Results A total of 1070 children were entered into the registry over 5 years. Two-thirds had a reaction to peanut. Children with peanut allergy were predominantly male (63%), white (78%), and with private health insurance (80%). Most reactions involved the skin (55%) and anaphylaxis occurred in 35%. The median age of a reaction was 1 year old. Atopic dermatitis was noted in 60% and asthma in 41%. Additional food allergy was noted in 58%. When second exposures occurred 28% had a more severe reaction. Skin test size did not differentiate the type of a reaction and children with anaphylaxis had slightly higher specific IgE levels. Severe reactions with inadvertent exposure in children who were peanut sensitized was rare ( Conclusions The strategies for peanut allergy prevention and treatment have evolved. The data obtained in this large registry can answer many questions that families and healthcare providers have during this transition.

AM Neophytou, SS Oh, MJ White. Thorax. 2018;73(11):1041–1048 To assess dose-response relationships between plasma cotinine–determined secondhand smoke (SHS) exposure and asthma outcomes in minority children. The study included 1172 Latino and African American children with asthma from the mainland and Puerto Rico. The investigators used subsamples of participants from the Gene-environments and Admixture in Latino Americans Study and the Study of African Americans, Asthma, Genes, and Environments. …

Background Leukotrienes are induced by viral infections. Objectives To determine whether treatment with montelukast would improve asthma disease control in patients with mild allergic asthma during an experimentally induced rhinovirus infection. Methods Patients with mild allergic asthma were randomized to receive treatment with either montelukast or placebo, and 7 days later both groups were inoculated with human rhinovirus 16. Patients were evaluated at baseline, during the acute infection phase, and during the recovery phase for asthma and cold symptoms by questionnaire. Sputum, nasal lavage fluid, and blood were analyzed for viral shedding and cellular inflammation, and peak expiratory flow was measured daily. Results A total of 19 patients (11 in the placebo group and 8 in the active group) completed the study. No significant differences were found in asthma control and cold symptom scores between the control and treatment groups. The change in peak expiratory flow from the randomization to acute illness phase was greater in the placebo group than the treatment group (mean, −22 vs 0 L/min; P = .05). During the recovery phase, the percentage of sputum eosinophils increased in the placebo group and remained at baseline levels in the montelukast group (median, 2.7% vs 0.2%; P = .05 between groups). Conclusions In this pilot study, montelukast did not improve asthma control or cold symptom scores caused by experimental rhinovirus infection. Analysis of secondary outcomes suggests that montelukast may prevent reductions in lung function and increases in sputum eosinophils caused by common cold infections. Further studies are needed to determine whether these effects are associated with clinically significant improvements in health outcomes during natural colds. Trial Registration clinicaltrials.gov Identifier: NCT00359073.

Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009–2010 flu season. Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma. Methods: One hundred and eighty children, 4–12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily. Viral diagnostics were performed for all nasal samples. Measurements and Main Results: One hundred and sixty-one children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal samples. The incidence of H1N1 infection was significantly higher in children with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95% confidence interval, 1.8–9; P < 0.001), but rates of human rhinovirus infection (90% each) and other viral infections (47 vs. 41%) were similar. In children with asthma, there was a nonsignificant trend for increased loss of asthma control during H1N1 infections compared with human rhinovirus infections (38 vs. 21%; odds ratio, 2.6; 95% confidence interval, 0.9–7.2; P = 0.07). Conclusions: During peak 2009 H1N1 flu season, children with asthma were infected almost twice as often with H1N1 compared with other respiratory viruses. H1N1 infection also caused increased severity of cold symptoms compared with other viral infections. Given the increased susceptibility of children with asthma to infection, these findings reinforce the need for yearly influenza vaccination to prevent infection, and raise new questions about the mechanism for enhanced susceptibility to influenza infection in asthma.

Clinical research findings indicate that there are synergistic interactions between allergy and viral infection that cause increased severity of asthma exacerbations. This article summarizes the current literature linking these 2 risk factors for asthma exacerbation, and reviews experimental data suggesting potential mechanisms for interactions between viral infection and allergy that cause asthma exacerbations. In addition, the authors discuss clinical evidence that treatment of allergic inflammation could help to reduce the frequency and severity of virus-induced exacerbations of asthma.

Background Detection of either viral or bacterial pathogens is associated with wheezing in children; however, the influence of both bacteria and viruses on illness symptoms has not been described. Objective We evaluated bacterial detection during the peak rhinovirus season in children with and without asthma to determine whether an association exists between bacterial infection and the severity of rhinovirus-induced illnesses. Methods Three hundred eight children (166 with asthma and 142 without asthma) aged 4 to 12 years provided 5 consecutive weekly nasal samples during September and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis were performed on all nasal samples. Results Detection rates were 53%, 17%, and 11% for H influenzae , S pneumoniae , and M catarrhalis , respectively, with detection of rhinovirus increasing the risk of detecting bacteria within the same sample (odds ratio [OR], 2.0; 95% CI, 1.4-2.7; P P = .02). In the absence of rhinovirus, S pneumoniae was associated with increased cold symptoms (mean, 2.7 [95% CI, 2.0-3.5] vs 1.8 [95% CI, 1.5-2.2]; P = .006) and moderate asthma exacerbations (18% [95% CI, 12% to 27%] vs 9.2% [95% CI, 6.7% to 12%]; P = .006). In the presence of rhinovirus, S pneumoniae was associated with increased moderate asthma exacerbations (22% [95% CI, 16% to 29%] vs 15% [95% CI, 11% to 20%]; P = .01). Furthermore, M catarrhalis detected alongside rhinovirus increased the likelihood of experiencing cold symptoms, asthma symptoms, or both compared with isolated detection of rhinovirus (OR, 2.0 [95% CI, 1.0-4.1]; P = .04). Regardless of rhinovirus status, H influenzae was not associated with respiratory symptoms. Conclusion Rhinovirus infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M catarrhalis and S pneumoniae contribute to the severity of respiratory tract illnesses, including asthma exacerbations.

Bagini JM, LeMasters GK, Ryan PH, et al. Pediatr Allergy Immunol. 2006:17:278–284 PURPOSE OF THE STUDY. To examine the impact of environmental tobacco smoke (ETS) and visible mold exposure on the development of allergic rhinitis, rhinitis, and upper respiratory infection (URI) in early infancy. STUDY POPULATION. Six hundred thirty-three infants ≥35 weeks’ gestation with at least 1 parent who had 1 of 12 selected allergy symptoms and a positive skin-prick–test result to at least 1 of 15 aeroallergens. METHODS. The child's birth certificate and a questionnaire format were used to collect demographic data and information on family smoking habits, family health history, pet ownership, day care attendance, breastfeeding, and the infants’ respiratory health history from birth to the time of enrollment. Parents were asked to complete monthly diaries to collect information on their child's upper respiratory symptoms. They must have completed 1 diary before the child's 12-month clinical examination. Allergic rhinitis was defined as having rhinitis symptoms not associated with a cold or chest infection at least once on any diary and a positive skin-prick–test result to ≥1 aeroallergen at the 12-month visit. Study personnel examined the home for mold exposure within 3 weeks of study enrollment. RESULTS. Infants were nearly 3 times more likely to have allergic rhinitis at 12 months of age (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.04–6.8) and twice as likely to have rhinitis (OR: 1.9; 95% CI: 1.1–3.2) when exposed to ≥20 cigarettes per day. Infants were 5 times more likely (OR: 5.1; 95% CI: 2.2–12) to have frequent URIs when exposed to high mold levels. Having older siblings was protective for development of rhinitis and allergic rhinitis at age 1. CONCLUSIONS. ETS exposure is associated with rhinitis and allergic rhinitis in infants. Mold may be a stronger risk factor for URI than ETS. REVIEWER COMMENTS. This is one of very few studies to have examined the relevance of home exposures in the first year of life and demonstrated that early environmental exposures likely play a significant role in respiratory health outcomes in infancy. One weakness of the study was the fact that ETS exposure and URI and rhinitis symptoms were collected by parental report and may be subject to significant recall bias or erroneous reporting. Nevertheless, these findings support the need for further research in the areas of early environmental-exposure interventions and the role of gene-environment interactions that affect respiratory health outcomes.