An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.

BACKGROUND: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While Fe(NO) measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of Fe(NO) in clinical practice. PURPOSE: To develop evidence-based guidelines for the interpretation of Fe(NO) measurements that incorporate evidence that has accumulated over the past decade. METHODS: We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach. RESULTS: The evidence related to the use of Fe(NO) measurements is reviewed and clinical practice recommendations are provided. CONCLUSIONS: In the setting of chronic inflammatory airway disease including asthma, conventional tests such as FEV(1) reversibility or provocation tests are only indirectly associated with airway inflammation. Fe(NO) offers added advantages for patient care including, but not limited to (1) detecting of eosinophilic airway inflammation, (2) determining the likelihood of corticosteroid responsiveness, (3) monitoring of airway inflammation to determine the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected nonadherence to corticosteroid therapy.

Discrepancy between clinical asthma control assessment tools and fractional exhaled nitric oxide.

BACKGROUND: Asthma is an inflammatory disease, yet clinical tools that evaluate asthma control do not include measures of inflammation. OBJECTIVE: To determine the correlation between fractional exhaled nitric oxide (FeNO) and each of 5 asthma control evaluation tools, namely, the Asthma Control Questionnaire (ACQ), the Asthma Control Test (ACT), the National Asthma Education and Prevention Program (NAEPP) goals of therapy, the Joint Task Force Practice Parameter (JTFPP) on attaining optimal asthma control, and the Global Initiative for Asthma (GINA) guidelines. METHODS: Patients 6 years or older who had asthma were clinically evaluated by an asthma specialist. Patients completed the ACT and ACQ and underwent spirometry and FeNO measurement. The physician was blinded to FeNO results until asthma control assessments were concluded. Correlations between FeNO level and each clinical evaluation tool were calculated. RESULTS: One hundred patients 6 to 86 years old were enrolled. No significant association was found between FeNO level and asthma control based on ACQ (P > .99), ACT (P = .53), NAEPP (P = .53), JTFPP (P = .30), or GINA (P = .86) criteria. Agreement was high among the NAEPP, the JTFPP, and GINA; moderate between the ACQ and the ACT; and poor to fair between the ACT or the ACQ and the other 3 tools. CONCLUSIONS: In addition to clinical evaluation, the incorporation of FeNO measurement in evaluating asthma is likely to lead to a more optimal pharmacotherapy, guidance in adjusting the dosage of anti-inflammatory agents, and positive long-term disease outcome.

Rethinking asthma from business to bedside.

OBJECTIVE: To explore the possible application of concepts, methods, and tools validated in the worlds of statistics, business, engineering, and system dynamics to improve insight and outcomes in asthma care. DATA SOURCES: Peer-reviewed articles, books, and other publications on the topic of asthma care, dating back to 1931, were retrieved using MEDLINE searches and other external sources. Searches were restricted to include only studies with human subjects and the English language as descriptors, and the terms used included the following: system dynamics, statistical process control charts, continual improvement, mental models, personal mastery, systems thinking, team learning, and shared vision. Personal author observations and experiences were also included. STUDY SELECTION: Review and original research studies that reported on these concepts were evaluated. RESULTS: Results show that the concepts behind these models may be transferred to the system of asthma care. Indeed, case studies have shown that control charts can be used to detect signals of improved or declined function in asymptomatic patients, monitor medication adverse effects and the effects of adding a new medication, and evaluate the effectiveness of different medication delivery systems. CONCLUSIONS: These concepts and tools can provide immeasurable value to the process of rethinking and redesigning asthma care. They have the potential to help physicians and patients alike in designing and executing systems of care that are capable of not only delivering better outcomes but also inviting commitment to the long-term care many require.

Novel allele of the endothelial nitric oxide synthase gene polymorphism in Caucasian asthmatics.

The purpose of the present study was to investigate an association of the endothelial nitric oxide synthase (eNOS) gene polymorphism with asthma. eNOS intron4 variable number of tandem repeats (27 bp repeats) genotypes were determined in asthma patients and control subjects using microplate PCR. The Caucasian Asthma patients displayed three alleles while Caucasian controls displayed only two alleles. However, African Americans displayed all three alleles in both asthma patients and controls. African American controls displayed significantly higher a allele, significantly lower b allele, as well as c allele than those in Caucasians. This was the first report to show that there was a novel eNOS genotype present in asthmatic patients but not in control subjects in the Caucasian Community. The novel allele which we termed the c allele, could be a significant risk factor in the etiology of asthma in Caucasians. This novel allele could be involved in higher levels of NO in our Caucasian asthmatics.