The Journal of Allergy and Clinical Immunology
Volume 121, Issue 4 , Pages 839-844, April 2008

Advances in the care of adults with asthma and allergy in 2007

  • Andrea J. Apter, MD, MSc

      Affiliations

    • Corresponding Author InformationReprint requests: Andrea J. Apter, MD, MSc, 829 Gates Building, Hospital of the University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104.

Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pa

Received 20 December 2007; received in revised form 27 December 2007; accepted 27 December 2007. published online 13 February 2008.

Article Outline

In 2007 the National Asthma Education and Prevention Program published the Expert Panel Report 3, updating its 1997 and 2002 guidelines for the diagnosis and management of asthma with new emphasis on assessment and attainment of control. This review focuses on the Journal articles published in 2007 pertaining to risk and impairment in adult asthma and interventions to improve its control.

Key words: Asthma, adults, atopy, health disparities, therapeutics, adherence, inhaled corticosteroids, omalizumab, pregnancy, menopause

Abbreviations used: AMA, Against medical advice, EPR-3, Expert Panel Report 3, FEV1pp, FEV1 percent predicted, ICS, Inhaled corticosteroid

 

As in previous years,1, 2, 3, 4 this summary highlights reports published in the Journal during 2007 on clinical advances in adult asthma and allergy, whereas the companion review provides the pediatric perspective. Especially relevant to both was the release of the Expert Panel Report 3 (EPR-3) of the National Asthma Education and Prevention Program5, 6 with its new emphasis on maintaining asthma control through evaluating impairment and risk. Much of the clinical research published in last year's Journal involved these areas and emerging therapeutics, as outlined. Key advances are summarized in Table I.

Table I. Key advances in the care of adults with asthma and allergy in 2007
1. EPR-3 recommends careful assessment of asthma control.
2. Atopic children are at increased risk for developing asthma.
3. Lung function diminishes over the time of transition to menopause.
4. NO2, produced by gas stoves, is likely an important indoor pollutant associated with asthma symptoms.
5. Sensitization to cockroach, dust mite, cat, mold, and mouse was not associated with asthma morbidity in urban adults.
6. The language preference of parents influences whether a child with symptoms is diagnosed with asthma.
7. Although patients are less likely to take all of their prescribed ICSs compared with montelukast, patients still benefited more from ICSs.
8. Hospitalized patients discharged AMA after an admission for asthma are more likely to have a relapse.
9. Except for patients with the most severe asthma, omalizumab is not cost-effective.
10. Women prescribed ICSs during pregnancy may not fill more than 1 prescription.

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Risk factors for asthma or respiratory symptoms 

Atopy 

Several studies produced evidence that further implicates atopy as a risk factor for asthma. Burgess et al7 report an association between allergic rhinitis and subsequent development of asthma in an Australian birth cohort. The presence of allergic rhinitis before age 7 years increased the risk of asthma 7-fold before adolescence, 4-fold at age 13 years, and 2-fold at 44 years; the association diminished thereafter. The strength of this study was its longitudinal nature and duration, whereas its major limitation was the use of self-reported or caretaker-reported allergic rhinitis and asthma as surrogates for physician-diagnosed disease. The investigators speculate that aggressive treatment of allergic rhinitis in early life might favorably alter subsequent asthma development and severity. The association of allergic rhinitis with asthma was also studied by Arbes et al8 by using data from the National Health and Nutrition Examination Survey, a US population-based survey that included skin prick tests with 10 allergens (cat, Alternaria, white oak, short ragweed, dust mite, Russian thistle, Bermuda grass, perennial rye, German cockroach, and peanut) in subjects 6 to 59 years old. Researchers found 56% of asthma cases in these relatively young individuals attributable to atopy with the percentage of atopic-associated asthma higher in male subjects, subjects with the highest education (perhaps because allergic rhinitis is more commonly recognized within this group9), and urban-dwellers. Sensitivity to cat, Alternaria, or white oak was independently and positively associated with asthma. In addition, Naqvi et al10 have found that higher IgE levels predict lower baseline lung function and more severe asthma among Americans of Latino or African descent.

Nevertheless, as Ownby and Joseph11 caution, although about half of all asthma is attributable to atopy, the other half is not. They emphasize that in contrast with asthma in atopic individuals, asthma in nonatopic persons begins later in life, affects predominantly female subjects, has different triggers, and is often more severe. Its mechanisms need to be understood better.

Menopause 

Real et al12 found that lung function diminishes over the transition to menopause. In 1274 European women age 45 to 56 years taking no exogenous sex hormones, FEV1 (−120 mL; 95% CI, −177 to −63 mL) and forced vital capacity values were significantly lower and respiratory symptoms higher among women who failed to menstruate during the previous 6 months, independent of smoking history. The correlation was even stronger among women with body mass index <23 kg/m2. Although the authors postulated hormonal changes were implicated, the cross-sectional design of this study does not allow causal inferences.

Environment 

Dust mites and endotoxin 

Rowe et al13 investigated whether the timing of exposure to allergen affects sensitization. Their study, which involved a birth cohort of 200 high-risk Australian infants, found only transient dust mite IgE production in the first months of life, in contrast with elevated levels of mite-specific IgE by 2 years of age, suggesting dust mite contact in the postnasal period is more allergenic than prenatal exposure. Exposure to high levels of dust mite during infancy increases the risk of asthma at age 7 years and late-onset wheeze, according to Celedon et al,14 who studied a birth cohort of children with atopic parents. Paradoxically, exposure to endotoxin appeared to increase both the risk of atopy in infancy and of wheezing between 1 and 7 years of age, which contradicts the hygiene hypothesis.

Other indoor allergens and pollutants 

Analyses of indoor air quality by Kattan et al15 using data from the National Cooperative Inner-City Asthma Study reveal high concentrations of NO2, a by-product of gas appliances, and environmental tobacco smoke. In this setting, exposure to NO2, but not environmental tobacco smoke, increases the risk of asthma symptoms, especially in colder months, suggesting that control of NO2 exposure might reduce asthma morbidity. The study data also indicate higher morbidity from asthma among children with cockroach sensitivity and exposure. However, a related study of adults from East Harlem by Wisnivesky et al16 found no association of sensitization to indoor allergens including cockroach, dust mite, cat, mold, or mouse with asthma morbidity. The investigators conclude that identifying and modifying other risk factors will be necessary to improve asthma morbidity among urban adults.

Social environment 

Mosnaim et al17 show that caregiver language preference can determine whether a child with symptoms has diagnosed asthma. The investigators distributed surveys for caregivers to 14,177 Hispanic Chicago schoolchildren age 6 to 12 years. Caregivers of children with diagnosed asthma were more likely to have completed the survey in English, whereas children of caregivers who completed the survey in Spanish were more likely to have undiagnosed—and presumably untreated—asthma symptoms. However, the study does not distinguish whether language itself, or other collinear acculturation, social, or economic barriers that were not considered, account for this outcome.

Gene-environment interactions 

To understand better the interaction of environment and family history (ie, physician-reported asthma in a first-degree relative) on asthma morbidity, Kuiper et al18 have examined the potential contribution of environmental factors, such as exposure to secondhand smoke, mite, cat, dog, and breast milk. They prospectively followed 221 Dutch infants with a family history of asthma and 308 infants without such a history during the first 2 years of life. Exposure to parental smoking and increased levels of Der p 1 in dust samples from the infants' homes magnified the family history effect, whereas breast-feeding reduced it.

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New insights into management and communication with patients 

Adherence 

Rand et al19 compared adherence to an inhaled corticosteroid (ICS) versus montelukast tablets and discovered, not surprisingly, that participants with asthma were more likely to use the pill than the inhaler. An unexpected finding was that even when ICS (fluticasone) use was suboptimal, a dose-response relationship could be observed with regard to the amount of ICS used and both asthma rescue-free days and FEV1 percent predicted (FEV1pp) when baseline FEV1pp was <86%. The dose-response relationship also was observed in the 36-week open-label period, suggesting that fluticasone is more effective than montelukast, and that more ICS is prescribed than may be needed or used.

Williams et al20 explored the role of unconventional socioenvironmental barriers to adherence by tracking the ICS prescription-writing data and pharmacy claims. Among African American patients, residential crime rates were negatively associated with adherence, independent of other socioeconomic factors. Thus, neighborhood characteristics, which are not traditionally included in medical studies, may be important determinants of health.21 Likewise, steps to improve the quality of neighborhood life should lead to better self-management of chronic illness such as asthma and outcomes.

Baptist et al22 conducted a case-control chart-review study of hospital admissions for asthma to compare patients who leave hospitals against medical advice (AMA) with those who had a medically approved discharge. AMA patients were younger and were more likely to be male, be poor, lack commercial medical insurance or receive Medicaid, or have had an intensive care unit admission for asthma. They were also more likely to have a relapse. For patients at risk for AMA discharge, successful provider-patient communication to determine and address the precipitants is important.

Special situations: Pregnancy 

Enriquez et al23 studied 140,299 pregnancies from the Tennessee Medicaid program, of which 6.5% of the women had asthma. Of these, 23% had an asthma hospitalization or emergency department visit, with these adverse events occurring twice as frequently in black women. Maternal asthma was associated with low-birthweight infants and, in a dose-dependent manner, with hypertensive disorders of pregnancy, membrane-related disorders, preterm labor, antepartum hemorrhage, and cesarean section. Of women who used ICS, only 28% filled more than 1 prescription.

Interventions to improve management 

The EPR-3 emphasizes a multifaceted approach that includes expanding patient education to all points of contact, such as the pharmacy and schools.5, 6 Basheti et al24 and other pharmacists showed that taking 2.5 minutes to check inhaler technique at the pharmacy improved drug delivery and quality of life, although technique declined over a period of 3 to 6 months. A limitation was the small pharmacist sample size: 120 were contacted, but only 31 consented to participate, and 27 completed the study. It is possible that only pharmacists who were most enthusiastic about the intervention participated. Jones et al25 enrolled 2185 children age 3 to 18 years to receive structured asthma management delivered from mobile clinics providing ongoing care at their schools. Although the investigators reported success in achieving control, maintenance was highly variable.

The EPR-3 also encourages clinician and health system support of the patient-clinician partnership. Borrelli et al26 describe a promising patient-centered counseling approach to behavioral change called Motivational Interviewing that may be integrated into patient encounters to enhance motivation for behavioral change leading to improved self-management. Research is underway testing the efficacy of such an approach in asthma.

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EPR-3 and asthma control 

Poor asthma control is associated with higher morbidity and lower disease-specific quality of life.6, 27 EPR-3 advises assessment of baseline asthma severity when initiating therapy, then monitoring asthma control while adjusting stepwise therapy to prevent functional impairment and minimize the risk of an exacerbation (Fig 1).5 EPR-3 has proposed using validated questionnaires to measure impairment.5, 6 Schatz et al28 demonstrated the reliability and validity of the Asthma Control Test administered by interactive telephone outreach and speech recognition technology. Liu et al29 reported the development of the Childhood Asthma Control test for children age 4 to 11 years, incorporating input from children (8 items) and their caretakers (13 items). The Lara Asthma Symptom Scale, an 8-item tool previously validated in English and Spanish to assess control of symptoms in children, was validated for a large heterogeneous population of English-speaking adults.30

  • View full-size image.
  • Fig 1. 

    Stepwise approach to management of asthma in patients ≥12 years of age. Reprinted from Busse WW. National Asthma Education and Prevention Program Report 3: guidelines for the diagnosis and management of asthma, summary report 2007. J Allergy Clin Immunol 2007;120:S1-S138.5

Nevertheless, a study by Yoo et al31 illustrates the limitations of self-reported outcomes, including questionnaires, for documenting asthma. Concordance of caretaker report with review of the medical record children followed at the Mayo Clinic found consistency of 89% for report of no asthma, but only 49% agreement for the presence of asthma. Caretakers tended to underreport the asthma status of their children.

Although tools that measure control of asthma are important for research and may be helpful in some clinical settings, a note of caution is warranted. They must be appropriate for the language and literacy of patients or caregivers, and they must address patients' chief complaints. Even a validated tool for data collection could be perceived by patients as a substitute for direct involvement by the physician.32

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Therapeutics 

Omalizumab 

The potential steroid-sparing benefit of omalizumab, the first biologic antiasthma agent approved by the US Food and Drug Administration, has been tempered by its cost. The economic analysis from a societal viewpoint according to the US Panel on Cost-Effectiveness in Health and Medicine by Wu et al33 found that except for patients with the most severe asthma, omalizumab is not cost-effective. Treatment with omalizumab costs more than $800,000 per quality-adjusted life-year gained, far in excess of the $50,000 per quality-adjusted life-year that is considered cost-effective in the United States. Krishnan and Gould34 point out that although EPR-3 now includes omalizumab as a treatment option (Fig 1),5 it is not very effective and does not represent a good value for the health care dollar. In addition, there are now concerns about its safety on the basis of postmarketing reports of anaphylaxis after administration.35, 36

Controller and other medications 

Menzies et al,37 also searching for a nonsteroidal anti-inflammatory for asthma, evaluated simvastatin on the basis of its anti-inflammatory and immune-modulating properties in other settings. Their month-long double-blind randomized crossover trial of 16 Scottish adults found no evidence of anti-inflammatory effect on exhaled nitric oxide levels or other parameters.38 The sample size was small, and subjects with more severe asthma dropped out during the run-in period when anti-inflammatory medications were discontinued before randomization.

Lung function declines more rapidly in patients with asthma than normal individuals over time. The study by de Marco et al39 showed that ICS attenuates this decline in FEV1 in a dose-dependent manner. This effect was greatest in subjects with high serum IgE who used an ICS for at least 4 years, suggesting particular benefit in allergic asthma.

Chipps et al40 have conducted an analysis of data from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens,41 a large cohort of difficult-to-treat children with asthma (≥2 urgent care visits or ≥2 prednisone bursts or prescribed more than 3 controller medications or using high-dose ICS or ≥5 mg prednisone/d in the past year), a study funded by the codevelopers of omalizumab. Investigators found that the subjects 6 to 17 years old who had the highest health care utilization and use were shorter and weighed more than their peers.40 Whether these deficits resulted from the disease, its treatment, or other factors is not clear from this cross-sectional analysis.

The safety of medications containing long-acting β-agonists continues to receive attention.42, 43, 44 Chinchilli45 reviewed a meta-analysis of the safety of salmeterol43 and discussed epidemiologic principles governing systematic reviews. One limitation of this meta-analysis is that findings reflect the results of 1 large study.42 The authors, by excluding unpublished studies such as abstracts of scientific meetings or data from pharmaceutical firms, may have omitted negative studies. By including only randomized placebo-controlled double-blind studies that compared salmeterol to placebo, only 19 of 5000 originally identified studies were included. Including other studies could have provided more data on adverse events of patients exposed to salmeterol.

Camargo et al46 describe significant regional differences in the prescribing of EpiPens, considered to be surrogate for anaphylaxis prevalence. Noting that New England has the highest frequency of EpiPen prescribing, whereas Hawaii the lowest, they theorize that sunlight-dependent vitamin D status could be an etiologic factor in anaphylaxis. Unanswered questions include, “Is the rate of epinephrine-prescribing truly reflective of the prevalence of anaphylaxis?,” “To what extent do other factors, especially social and economic, explain regional prescribing practices?” or “Would this regional difference persist if other brands of injectible epinephrine were included?” The data are provided by Dey (Napa, Calif), the manufacturer of EpiPen. It is well to remember that a statistical association, for example between vitamin D status and anaphylaxis occurrence, does not imply causality, as is noted by Taback and Simons47 in their editorial.

Kemeny et al48 remind us to be ever mindful of the placebo effect. In their double-blind crossover study of 55 adults with mild asthma, bronchial hyperreactivity to methacholine was significantly reduced in 18% of subjects by placebo bronchodilator.

Biomarkers for assessing success of therapy 

Biomarkers continue to generate interest as tools for assessing asthma severity and control, although EPR-3 does not recommend them for clinical application, citing an insufficient current research consensus. Several novel biomarkers were described in early investigations in 2007. The difference between inspiratory and expiratory attenuation from high-resolution computed tomography of the chest, the air trapping index, was studied as a potential biomarker of active asthma, because it appears to reflect involvement of the small airways. A 3-month trial of ICSs resulted in decreased airtrapping.49 Dragonieri et al50 propose that volatile organic compounds in exhaled breath are quantitatively different in healthy individuals and individuals with asthma and could be used for diagnosis and outcomes measurement. However, volatile organic compound concentrations failed to distinguish mild from severe asthma.

Bourdin et al51 detect reticular basement membrane thickening compatible with airway remodeling in endobronchial biopsy specimens from individuals with severe asthma. When compared with bronchial specimens from subjects with mild asthma or chronic obstructive pulmonary disease, the biopsies from individuals with severe asthma showed greater basement membrane thickness. The obvious limitation of this approach for clinical assessment is its invasiveness. De Lange et al52 used hyperpolarized helium-3 magnetic resonance to image airspaces and focal areas of airflow obstruction over time and with methacholine challenge in 10 individuals with asthma. Both recurrent and persistent regional ventilation defects were observed, suggesting the existence of regions of relatively fixed obstruction.

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Future research 

Simons53 reports that 65% of a random sample of abstracts presented at the 2000 American Academy of Allergy, Asthma & Immunology Annual Meeting were subsequently published as full-text articles in peer-reviewed journals, a higher ratio than is reported by many specialties and other subspecialties. She recommends continued monitoring of abstract performance, because determining the reasons for failure to publish may serve as opportunities for mentoring young investigators. Finally, in recounting the remarkable accomplishments of the Asthma and Allergic Disease Centers funded by the National Institute of Allergy and Infectious Diseases, Austen54 reminds us of the importance of research to the future of our field and of engaging and supporting the next generation.

Conclusion 

This year's research achievements and the EPR-3 update focus attention on asthma control. This requires attention to allergic and nonallergic factors, special life events including pregnancy and menopause, the indoor environment, social issues including language discordance with clinicians, and reasons for poor adherence. Further study of these factors will be the substrate for the research of the next generation.

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I thank Anita T. Gewurz, MD, for her dedicated review and thoughtful suggestions.

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References 

  1. Apter AJ, Szefler SJ. Advances in adult and pediatric asthma. J Allergy Clin Immunol. 2006;117:512–518
  2. Apter AJ, Szefler SJ. Advances in adult and pediatric asthma. J Allergy Clin Immunol. 2004;113:407–414
  3. Szefler SJ, Apter A. Advances in pediatric and adult asthma. J Allergy Clin Immunol. 2005;115:470–477
  4. Apter AJ. Advances in adult asthma 2006: its risk factors, course, and management. J Allergy Clin Immunol. 2007;119:563–566
  5. Busse WW. National Asthma Education and Prevention Program Report 3: guidelines for the diagnosis and management of asthma, summary report 2007. J Allergy Clin Immunol. 2007;120:S1–S138
  6. National Institutes of Health . National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. Washington (DC): NIH; 2007;NIH publication no. 07-4051
  7. Burgess JA, Walters EH, Byrnes GB, Matheson MC, Jenkins MA, Wharton CL, et al. Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: a longitudinal study. J Allergy Clin Immunol. 2007;120:863–869
  8. Arbes SJ, Gergen PJ, Baughn B, Zeldin DC. Asthma cases attributable to atopy: results from the third National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2007;120:1139–1145
  9. Litonjua AA, Celedon JC, Hausmann J, Nikolov M, Sredl D, Ryan L, et al. Variation in total and specific IgE: effects of ethnicity and socioeconomic status. J Allergy Clin Immunol. 2005;115:751–757
  10. Naqvi M, Choudhry S, Tsai HJ, Thyne S, Navarro D, Nazario S, et al. Association between IgE levels and asthma severity among African American, Mexican, and Puerto Rican patients with asthma. J Allergy Clin Immunol. 2007;120:137–143
  11. Ownby DR, Joseph CL. Should non-atopic asthma get equal attention?. J Allergy Clin Immunol. 2007;120:1018–1020
  12. Real FG, Svanes C, Omenaas ER, Antò JM, Plana E, Jarvis D, et al. Lung function, respiratory symptoms, and the menopausal transition. J Allergy Clin Immunol. 2007;Oct 26 [epub ahead of print]
  13. Rowe J, Kusel M, Holt BJ, Suriyaarachchi D, Serralha M, Hollams E, et al. Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort. J Allergy Clin Immunol. 2007;119:1164–1173
  14. Celedon JC, Milton DK, Ramsey CD, Litonjua AA, Ryan L, Platts-Mills TA, et al. Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood. J Allergy Clin Immunol. 2007;120:144–149
  15. Kattan M, Gergen PJ, Eggleston P, Visness CM, Mitchell HE. Health effects of indoor nitrogen dioxide and passive smoking on urban asthmatic children. J Allergy Clin Immunol. 2007;120:618–624
  16. Wisnivesky JP, Sampson H, Berns S, Kattan M, Halm EA. Lack of association between indoor allergen sensitization and asthma morbidity in inner-city adults. J Allergy Clin Immunol. 2007;120:113–120
  17. Mosnaim GS, Sadowski LS, Durazo-Arvizu RA, Sharp LK, Curtis LM, Shalowitz MU, et al. Parental language and asthma among urban Hispanic children. J Allergy Clin Immunol. 2007;120:1160–1165
  18. Kuiper S, Muris JW, Dompeling E, Kester AD, Wesseling G, Knottnerus JA, et al. Interactive effect of family history and environmental factors on respiratory tract-related morbidity in infancy. J Allergy Clin Immunol. 2007;120:388–395
  19. Rand C, Bilderback A, Schiller K, Edelman JM, Hustad CM, Zeiger RS. Adherence with montelukast or fluticasone in a long-term clinical trial: results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial. J Allergy Clin Immunol. 2007;119:916–923
  20. Williams LK, Joseph CL, Peterson EL, Moon C, Xi H, Krajenta R, et al. Race-ethnicity, crime, and other factors associated with adherence to inhaled corticosteroids. J Allergy Clin Immunol. 2007;119:168–175
  21. Gergen PJ, Apter AJ. Unconventional risk factors: another pathway to understanding health disparities. J Allergy Clin Immunol. 2007;119:165–167
  22. Baptist AP, Warrier I, Arora R, Ager J, Massanari RM. Hospitalized patients with asthma who leave against medical advice: characteristics, reasons, and outcomes. J Allergy Clin Immunology. 2007;119:924–929
  23. Enriquez R, Griffin MR, Carroll KN, Wu P, Cooper WO, Gebretsadik T, et al. Effect of maternal asthma and asthma control on pregnancy and perinatal outcomes. J Allergy Clin Immunol. 2007;120:625–630
  24. Basheti IA, Reddel HK, Armour CL, Bosnic-Anticevich SZ. Improved asthma outcomes with a simple inhaler technique intervention by community pharmacists. J Allergy Clin Immunol. 2007;119:1537–1538
  25. Jones CA, Clement LT, Morphew T, Kwong KY, Hanley-Lopez J, Lifson F, et al. Achieving and maintaining asthma control in an urban pediatric disease management program: the Breathmobile Program. J Allergy Clin Immunol. 2007;119:1445–1453
  26. Borrelli B, Riekert KA, Weinstein A, Cardella L. Brief motivational interviewing as a clinical strategy to promote asthma medication adherence. J Allergy Clin Immunol. 2007;120:1023–1030
  27. Chen H, Gould MK, Blanc PD, Miller DP, Kamath TV, Lee JH, et al. Asthma control, severity, and quality of life: quantifying the effect of uncontrolled disease. J Allergy Clin Immunol. 2007;120:396–402
  28. Schatz M, Zeiger RS, Drane A, Harden K, Cibildak A, Oosterman JE, et al. Reliability and predictive validity of the Asthma Control Test administered by telephone calls using speech recognition technology. J Allergy Clin Immunol. 2007;119:336–343
  29. Liu AH, Zeiger R, Sorkness C, Mahr T, Ostrom N, Burgess S, et al. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol. 2007;119:817–825
  30. Wood PR, Smith B, O'Donnell L, Galbreath AD, Lara M, Forkner E, et al. Quantifying asthma symptoms in adults: the Asthma Symptom Scale. J Allergy Clin Immunol. 2007;120:1368–1372
  31. Yoo K, Johnson SK, Voigt RG, Campeau LJ, Yawn BP, Juhn YJ. Characterization of asthma status by parent report and medical record review. J Allergy Clin Immunol. 2007;120:1468–1469
  32. Apter AJ. Reply. J Allergy Clin Immunol. 2007;120:729
  33. Wu AC, Paltiel D, Kuntz KM, Weiss ST, Fuhlbrigge AL. Cost-effectiveness of omalizumab in adults with severe asthma: results from the Asthma Policy Model. J Allergy Clin Immunol. 2007;120:1146–1152
  34. Krishnan JA, Gould M. Omalizumab for severe allergic asthma: dollars and sense. J Allergy Clin Immunol. 2007;120:1015–1017
  35. Omalizumab (for subcutaneous use) (marketed as Xolair). 2007. Bethesda (MD): US Food and Drug Administration. Available at: http://www.fda.gov/cder/drug/InfoSheets/HCP/omalizumabHCP.pdf. Accessed December 26, 2007.
  36. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol. 2007;120:1378–1381
  37. Menzies D, Nair A, Meldrum KT, Fleming D, Barnes M, Lipworth BJ. Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma. J Allergy Clin Immunol. 2007;119:328–335
  38. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171:912–930
  39. de Marco R, Marcon A, Jarvis D, Accordini S, Bugiani M, Cazzoletti L, et al. Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE. J Allergy Clin Immunol. 2007;119:611–617
  40. Chipps BE, Szefler SJ, Simons FE, Haselkorn T, Mink DR, Deniz Y, et al. Demographic and clinical characteristics of children and adolescents with severe or difficult-to-treat asthma. J Allergy Clin Immunol. 2007;119:1156–1163
  41. Dolan CM, Fraher KE, Bleecker ER, Borish L, Chipps B, Hayden ML, et al. Design and baseline characteristics of the epidemiology and natural history of asthma: Outcomes and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma. Ann Allergy Asthma Immunol. 2004;92:32–39
  42. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15–26
  43. Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006;144:904–912
  44. Szefler SJ, Whelan GJ, Leung DY. “Black box” warning: wake-up call or overreaction?. J Allergy Clin Immunol. 2006;117:26–29
  45. Chinchilli VM. General principles for systematic reviews and meta-analyses and a critique of a recent systematic review of long-acting beta-agonists. J Allergy Clin Immunol. 2007;119:303–306
  46. Camargo CA, Clark S, Kaplan MS, Lieberman P, Wood RA. Regional differences in EpiPen prescriptions in the United States: the potential role of vitamin D. J Allergy Clin Immunol. 2007;120:131–136
  47. Taback SP, Simons FE. Anaphylaxis and vitamin D: a role for the sunshine hormone?. J Allergy Clin Immunol. 2007;120:128–130
  48. Kemeny ME, Rosenwasser LJ, Panettieri RA, Rose RM, Berg-Smith SM, Kline JN. Placebo response in asthma: a robust and objective phenomenon. J Allergy Clin Immunol. 2007;119:1375–1381
  49. Tunon-de-Lara JM, Laurent F, Giraud V, Perez T, Aguilaniu B, Meziane H, et al. Air trapping in mild and moderate asthma: effect of inhaled corticosteroids. J Allergy Clin Immunol. 2007;119:583–590
  50. Dragonieri S, Schot R, Mertens BJ, Le Cessie S, Gauw SA, Spanevello A, et al. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol. 2007;120:856–862
  51. Bourdin A, Neveu D, Vachier I, Paganin F, Godard P, Chanez P. Specificity of basement membrane thickening in severe asthma. J Allergy Clin Immunol. 2007;119:1367–1374
  52. de Lange EE, Altes TA, Patrie JT, Parmar J, Brookeman JR, Mugler JP, et al. The variability of regional airflow obstruction within the lungs of patients with asthma: assessment with hyperpolarized helium-3 magnetic resonance imaging. J Allergy Clin Immunol. 2007;119:1072–1078
  53. Simons FE. Eventual full-text publication of research abstracts presented at an allergy/immunology meeting. J Allergy Clin Immunol. 2007;119:499–501
  54. Austen KF. The National Institute of Allergy and Infectious Diseases' Asthma and Allergic Disease Centers: a personal commentary. J Allergy Clin Immunol. 2007;119:34–35

 Supported by R01 HL073932 and K02 HL088469.

 Disclosure of potential conflict of interest: A. J. Apter has received research support from the National Heart, Lung, and Blood Institute.

PII: S0091-6749(08)00006-7

doi:10.1016/j.jaci.2007.12.1176

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 4 , Pages 839-844, April 2008

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