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Background The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining “exacerbation,” or about how to characterize an episode’s severity. Objective National Institutes of Health (NIH) institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies. Methods We utilized comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes, and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011. Results No dominant definition of “exacerbation” was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalization, and (3) use of short-acting β-agonists (SABAs) as quick-relief (sometimes referred to as “rescue” or “reliever”) medications. Conclusions The working group participants propose that the definition of “asthma exacerbation” be “a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome.” As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Further, they propose the development of a standardized, component-based definition of “exacerbation” with clear thresholds of severity for each component.

Allergic disease prevalence has significantly increased in recent decades. Primary prevention efforts are being guided by the study of the exposome, or collective environmental exposures beginning during the prenatal period, to identify modifiable factors that impact allergic disease risk. In this review, we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their impact on atopy development, focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life may also impact disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all individuals. Understanding the impact of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children.

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Rationale: Chronic bronchitis (CB) is characterized by persistent cough and sputum production. Studies were performed to test whether mucus hyperconcentration and increased partial osmotic pressure, in part caused by abnormal purine nucleotide regulation of ion transport, contribute to the pathogenesis of CB.Objectives: We tested the hypothesis that CB is characterized by mucus hyperconcentration, increased mucus partial osmotic pressures, and reduced mucus clearance.Methods: We measured in subjects with CB as compared with normal and asymptomatic smoking control subjects indices of mucus concentration (hydration; i.e., percentage solids) and sputum adenine nucleotide/nucleoside concentrations. In addition, sputum partial osmotic pressures and mucus transport rates were measured in subjects with CB.Measurements and Results: CB secretions were hyperconcentrated as indexed by an increase in percentage solids and total mucins, in part reflecting decreased extracellular nucleotide/nucleoside concentrations. CB mucus generated concentration-dependent increases in partial osmotic pressures into ranges predicted to reduce mucus transport. Mucociliary clearance (MCC) in subjects with CB was negatively correlated with mucus concentration (percentage solids). As a test of relationships between mucus concentration and disease, mucus concentrations and MCC were compared with FEV 1 , and both were significantly correlated.Conclusions: Abnormal regulation of airway surface hydration may slow MCC in CB and contribute to disease pathogenesis.

Rationale: Exposure to ozone causes a decrease in spirometric lung function and an increase in airway inflammation in healthy young adults at concentrations as low as 0.08 ppm, close to the National Ambient Air Quality Standard for ground level ozone. Objectives: To test whether airway effects occur below the current ozone standard and if they are more pronounced in potentially susceptible individuals, such as those deficient in the antioxidant gene glutathione S-transferase mu 1 (GSTM1). Methods: Pulmonary function and subjective symptoms were measured in 59 healthy young adults (19-35 yr) immediately before and after exposure to 0.0 (clean air, CA) and 0.06 ppm ozone for 6.6 hours in a chamber while undergoing intermittent moderate exercise. The polymorphonuclear neutrophil (PMN) influx was measured in 24 subjects 16 to 18 hours postexposure. Measurements and Main Results: Subjects experienced a significantly greater (P 5 0.008) change in FEV 1 (6 SE) immediately after exposure to 0.06 ppm ozone compared with CA (21.71 6 0.50% vs. 20.002 6 0.46%). The decrement in FVC was also greater (P 5 0.02) after ozone versus CA (22.32 6 0.41% vs. 21.13 6 0.34%). Similarly, changes in %PMN were greater after ozone (54.0 6 4.6%) than CA (38.3 6 3.7%) exposure (P , 0.001). Symptom scores were not different between ozone versus CA. There were no significant differences in changes in FEV 1 , FVC, and %PMN between subjects with GSTM1-positive and GSTM1-null genotypes. Conclusions: Exposure of healthy young adults to 0.06 ppm ozone for 6.6 hours causes a significant decrement of FEV 1 and an increase in neutrophilic inflammation in the airways. GSTM1 genotype alone appears to have no significant role in modifying the effects.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.

Ozone may play a significant role in the exacerbation of airway disease in asthmatics, either by priming the airway mucosa such that cellular responses to allergen are enhanced or by exerting an intrinsic effect on airway inflammation. Previous investigations of nonasthmatic subjects revealed that ozone induces both nasal and bronchial inflammation, suggesting that nasal responses to ozone may be used as a surrogate marker for the effect of this pollutant on bronchial mucosal inflammation. In this study, the effect of exposure to 0.4 ppm ozone on nasal inflammation in 11 allergic asthmatics sensitive to Dermatophygoides farinae was examined. This study was designed such that the effect of ozone exposure on the late-phase reaction to allergen was emphasized, using eosinophil influx and changes in eosinophil cationic protein as principal endpoints. By employing a "split-nose" design, in which allergen was applied to only one side of the nose while saline was applied to the contralateral side, both the effect of ozone on nasal inflammation due to allergen challenge as well as its direct action on non-allergen-challenged nasal tissues was examined. The results reported herein indicate that ozone exposure has both a priming effect on allergen-induced responses as well as an intrinsic inflammatory action in the nasal airways of perennially allergic asthmatics.