Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma.

RATIONALE: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. OBJECTIVES: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. METHODS: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. MEASUREMENTS AND MAIN RESULTS: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10-9; odds ratio, 2.8; 95% confidence interval, 2.0-4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. CONCLUSIONS: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575).

Ambient air pollution, lung function, and airway responsiveness in asthmatic children.

BACKGROUND: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking. OBJECTIVE: We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. METHODS: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders. RESULTS: Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20. CONCLUSIONS: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

Preparing the Allergist/Immunologist for the Next Pandemic.

The COVID-19 pandemic had a profound impact on society in general and allergists' practices in particular. The adverse effects included a loss of practice productivity and income, staffing, and in-office procedures due to concerns about the spread of infection and the need for social/physical distancing as well as isolation. Allergy training programs and research activities also suffered. Federal financial assistance, rapid adoption of telehealth with Medicare waivers, and adaptation of practice sites, training programs, and research activities allowed for some return to normal, although still with significant restrictions in staffing and in-office procedures. There were positive aspects to the pandemic in the form of telehealth initiatives, pathways for rapid development and approval of tests and treatments, opportunities for new collaborations, and expertise in vaccines. Preparation for the next pandemic needs to be considered now to avoid the mistakes and missteps that occurred with the COVID-19 pandemic. On a national level, a strategy to overcome the societal divisions, misinformation/disinformation, and distrust of science needs to be developed based on better communication, as well as advocacy for continued improvement in our public health system. Practices and training programs as well as research centers need to institutionalize changes made during the pandemic so they can quickly be reinitiated when necessary.

Pharmacologic Management of Chronic Urticaria in Pediatric Patients: The Gap Between Guidelines and Practice.

Chronic urticaria is an uncommon disorder in children but can present considerable morbidity, as well as frustration for the healthcare provider and parent. The prevalence is 0.1-0.3% but can vary considerably by country. Chronic spontaneous urticaria (no identifiable cause) is responsible for 70-80% of chronic urticaria, about half of this due to a subtype called chronic autoimmune urticaria identified by the presence of autoantibodies to IgE or the IgE receptor. Chronic urticaria that is triggered by external physical stimuli is called chronic inducible urticaria and is present in another 15-20%. Allergies, infection, and other underlying diseases such as thyroid disease, celiac disease, or Helicobacter pylori infection cause a minor proportion of cases. Chronic urticaria has considerable impact on quality of life and healthcare costs. An adverse impact on quality of life is more prevalent in older children and adolescents and can be comparable to other diseases of childhood such as diabetes and epilepsy. Healthcare costs can be 50% higher than the national estimates for healthy patients and include more hospitalizations, longer duration of hospitalizations, and more emergency department (ED) and outpatient visits. Allergic and autoimmune diseases can be comorbidities that add to healthcare utilization. Resolution can take years. Guidelines are available for diagnosis and treatment. A good history is the key to identifying the cause. Minimal laboratory tests are required and should be guided by the history. Patients with easily controlled urticaria may not need any laboratory tests. Suggested treatment emphasizes the use of non-sedating antihistamines, utilized in a step-wise fashion beginning with normal doses and advancing the dose based on the response up to four times the recommended dose for age. Other treatments are left to the urticaria specialist and are not discussed in this paper. These guidelines are not well utilized based on real-world studies; sedating antihistamines and oral steroids are overutilized. Medications should be taken daily, not as needed. Additional medications, if required, should be added to prior medications in a step-wise fashion. The gap between the guidelines for diagnosis and treatment and what is happening in the real world needs to be closed to reduce the cost and morbidity associated with this disorder.

Treatment Patterns, Healthcare Resource Utilization, and Spending Among Medicaid-Enrolled Children with Chronic Idiopathic/Spontaneous Urticaria in the United States.

INTRODUCTION: Few studies have described chronic idiopathic/spontaneous urticaria (CIU/CSU) healthcare burden in adults, while this information remains largely unknown in children. We aimed to describe treatment patterns, healthcare resource utilization (HRU), and costs in CIU/CSU pediatric patients, as well as to compare HRU and costs in CIU/CSU and CIU/CSU-free pediatric patients. METHODS: Medicaid claims from four states (09/01/2013-03/31/2016) were used to identify patients less than 12 years old. The CIU/CSU cohort included patients with either at least two claims for idiopathic, other, or unspecified urticaria at least 6 weeks apart, or at least one claim for urticaria and at least one claim for angioedema at least 6 weeks apart (index date defined as the first claim). The control cohort included patients without urticaria/angioedema claims (index date randomly assigned). Patients without at least 6 months of continuous Medicaid eligibility pre- and post-index were excluded. HRU and costs were compared between propensity score-matched cohorts during the post-index follow-up. RESULTS: A total of 548 CIU/CSU patients (mean [SD] age 4.5 [3.3] years; 51.3% male) were matched 1:1 with controls. In the CIU/CSU cohort, 51.8% used non-sedating prescription H1-antihistamines, 24.3% used oral corticosteroids, and 23.5% used other prescription H1-antihistamines; 13.5% consulted allergist/immunologists and 2.4% consulted dermatologists in the first 6 months of follow-up. Compared to controls, CIU/CSU patients had significantly more per patient per year (PPPY) inpatient (incidence rate ratio [IRR] 2.05), outpatient (IRR 2.20), and emergency department (IRR 1.64) visits (all p values < 0.05). Moreover, CIU/CSU patients also had significantly higher PPPY healthcare costs (mean cost difference [MCD] $1853), driven by incremental outpatient (MCD $1286) costs (all p values < 0.01). CONCLUSIONS: CIU/CSU pediatric patients had low use of non-sedating H1-antihistamines and high use of oral corticosteroids. Compared to CIU/CSU-free controls in the same age group, CIU/CSU pediatric patients had higher HRU and healthcare costs. FUNDING: Novartis Pharmaceuticals Corporation.

Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years.

OBJECTIVE: To update the American Academy of Pediatrics clinical practice guideline regarding the diagnosis and management of acute bacterial sinusitis in children and adolescents. METHODS: Analysis of the medical literature published since the last version of the guideline (2001). RESULTS: The diagnosis of acute bacterial sinusitis is made when a child with an acute upper respiratory tract infection (URI) presents with (1) persistent illness (nasal discharge [of any quality] or daytime cough or both lasting more than 10 days without improvement), (2) a worsening course (worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement), or (3) severe onset (concurrent fever[temperature ≥39°C/102.2°F] and purulent nasal discharge for at least 3 consecutive days). Clinicians should not obtain imaging studies of any kind to distinguish acute bacterial sinusitis from viral URI, because they do not contribute to the diagnosis; however, a contrast-enhanced computed tomography scan of the paranasal sinuses should be obtained whenever a child is suspected of having orbital or central nervous system complications. The clinician should prescribe antibiotic therapy for acute bacterial sinusitis in children with severe onset or worsening course. The clinician should either prescribe antibiotic therapy or offer additional observation for 3 days to children with persistent illness. Amoxicillin with or without clavulanate is the firstline treatment of acute bacterial sinusitis. Clinicians should reassess initial management if there is either a caregiver report of worsening(progression of initial signs/symptoms or appearance of new signs/symptoms) or failure to improve within 72 hours of initial management.If the diagnosis of acute bacterial sinusitis is confirmed in a child with worsening symptoms or failure to improve, then clinicians may change the antibiotic therapy for the child initially managed with antibiotic or initiate antibiotic treatment of the child initially managed with observation. CONCLUSIONS: Changes in this revision include the addition of a clinical presentation designated as "worsening course," an option to treat immediately or observe children with persistent symptoms for 3 days before treating, and a review of evidence indicating that imaging is not necessary in children with uncomplicated acute bacterial sinusitis.

Population-based screening or case detection for asthma: are we ready?

Asthma is a prevalent health problem for which there are effective treatments. By identifying people with asthma and treating them effectively, the burden of asthma in the United States should be reduced. Detecting people with asthma through screening programs seems a logical approach to the problem. This article assesses our readiness for population-based screening and case detection programs for asthma and examines these activities in relation to World Health Organization criteria for determining the appropriateness of screening programs. Given that, at this time, a number of the criteria have not been met, we conclude that population-based approaches to screening and case detection of asthma are of unproven benefit and need further research. A more appropriate focus may be to ensure that all people who are diagnosed with asthma receive appropriate medical care.