ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Context Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. It is not known whether treatment of GER with a proton-pump inhibitor (PPI) improves asthma control. Objective To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. Design, Setting, and Patients A multicenter, randomized, masked, placebo controlled, parallel clinical trial comparing lansoprazole to placebo in children with poor asthma control on inhaled corticosteroid treatment conducted at 18 academic clinical centers. Participants were followed for 24 weeks. A subgroup had an esophageal pH study before randomization. Intervention Children received either lansoprazole (15 mg daily < 30 kg; 30 mg ≥ 30 kg) or placebo, 1:1 allocation ratio. Main outcome The primary outcome was the change in Asthma Control score (ACQ, range from 0 to 6). Secondary outcomes included lung function measures, asthma-related quality of life and acute episodes of poor asthma control. Results 306 children were enrolled from April 2011 to August 2010, the median age was 11. The mean change (95% confidence interval (CI)) in the ACQ score was −0.1 (−0.2, 0.1) and −0.2 (−0.4, −0.1) units for the lansoprazole and placebo groups, respectively (P=0.12). There were no detectable treatment differences in secondary outcomes (mean (95% CI) for FEV1(0.00 (−0.08, 0.08)), asthma quality of life (−0.1 (−0.4, 0.1) or episodes of poor asthma control, hazard ratio of 1.18 (95% CI 0.91, 1.53). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole versus placebo was observed for any asthma outcome. Children treated with lansoprazole reported more upper respiratory infections (63% vs 49%, P=0.02), sore throats (52% vs 39%, P=0.02), and bronchitis (7% vs 2%, P=0.05). Conclusion Among children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, as compared to placebo, did not improve symptoms nor lung function but was associated with increased adverse events.

The role of oxidative stress in asthma is gaining increasing scientific attention. The hallmark of asthma is airway inflammation. Oxidative stress may initiate and augment inflammation, and may also result from inflammation. Exposure to tobacco smoke, ozone, diesel exhaust, and a variety of other pollutants generates reactive oxygen species and other oxidative stressors. Some studies suggest that asthmatics have a decreased ability to respond to oxidative stress, while others find upregulated antioxidative function. Oxidative stress may alter the Th(1)/Th(2) immune response and result in activation of NF-kbeta, a powerful inducer of pro-inflammatory genes. Genetic polymorphisms may play an important role in determining susceptibility to oxidative stress. Many therapeutic strategies to decrease oxidative stress in asthma have been suggested. Dietary changes, antioxidant vitamins, other antioxidant drugs, Ayurvedic supplements, and even radon exposure in a hot bathroom have been studied. Minimizing exposure of young children to environmental tobacco smoke remains paramount.

There is no consensus about reproducibility and reliability of spirometry in young children. We evaluated forced expiratory maneuvers from 98 children aged 3 to 5 years with a variety of respiratory disorders before and after bronchodilator treatment. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were analyzed for reproducibility by the American Thoracic Society criteria and for reliability based on the coefficient of variation (CV%). Over 90% of the patients cooperated, however, while 95% could exhale for at least 1 second, very few generated an FEV1 on all 6 "best" efforts. This clearly improved with age. Of all patients nearly 60% performed reproducible pre- and postbronchodilator sets of FVC but only 32% performed reproducible sets of FEV1. Based on the CV%, those patients who could reproducibly perform an FVC and FEV1 did it quite reliably (mean CV%, 9.38 and 7.01 for FVC and FEV1, respectively). We conclude that while some very young children can perform spirometry, reliability of performance cannot be assumed in this age group.

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To determine if micronutrient intake is associated with asthma severity, we administered the Block food frequency questionnaire to participants in a randomized clinical trial of the safety of influenza vaccine for asthmatics. The nutrition substudy included 1033 participants, aged 12-75. Intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber was compared with asthma severity at baseline [forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEF), asthma symptoms] and the rate of asthma exacerbations during the 2 weeks following influenza vaccination. The only nutrient that had a consistent association with asthma severity was genistein, a soy isoflavone. None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders. The FEV1 in genistein consumers of at least 250 microg/1000 Kcal/day was 82.1% predicted, 79.9% predicted for those who consumed between 1 and 249 microg/1000 kcal, and 76.2% predicted in genistein nonconsumers (p=0.006); the PEF was 82.7% predicted, 80.8% predicted, and 78.3% predicted, respectively (p=0.009). There were no differences in the Asthma Symptom Utility Index (ASUI). We could not account for these results based on differences in demographics, body mass index, or consumption of other nutrients. Thus, increasing consumption of genistein is associated with better lung function in patients with asthma. Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity.

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