Correlations between exhaled nitric oxide, rs28364072 polymorphism of FCER2 gene, asthma control, and inhaled corticosteroid responsiveness in children with asthma.

In children with asthma, the responsiveness of inhaled corticosteroids (ICS) is depended on asthma endotype and phenotype. This study aimed to describe the clinical and biological characteristics, and its correlation with polymorphism of rs28364072 in FCER2 of asthmatic children. This work aimed to study the correlation between fractional concentration of exhaled nitric oxide (FENO) level and rs28364072 polymorphism of FCER2 gene with ICS responsiveness and disease control in children with asthma. This study was a prospective and descriptive study. All clinical characteristics, FENO, blood eosinophil counts (BEC), skin prick test (SPT), total IgE, asthma control test, and FCER2 gene polymorphism were performed for each patient. One hundred and seven asthmatic children who were over 5 years old (9.2 ± 2.6), were included. Patients with FENO > 20 ppb had higher percentage of positive SPT, total IgE level, and BEC (89.2 vs 80.0%, 851.1 vs 656.9 UI ml-1, and 785 ± 576 G L-1 vs 425 ± 364 G L-1; respectively). Among them, there were 54.2% of homozygous TT, 36.4% of heterozygous TC, and 9.4% of homozygous CC of rs28364072 polymorphism in FCER2. The percentage of patients with controlled asthma was increasing after 1 month and 3 months (47.1% and 58.8%; respectively). During the study, the ICS was decreasing as indicated by asthma control (348 ± 118 mcg at 1st month vs 329 ± 119 mcg at 3rd month; p < 0.05). CC genotype had the lowest level of increasing FEV1 compared to that in genotype TC and TT (8.4% vs 8.7% and 27.1%; p > 0.05 and p < 0.05; respectively). The percentage of polymorphism in rs28364072 of FCER2 was significant higher in patients with controlled asthma compared to uncontrolled asthma. Asthmatic children with high FENO and rs28364072 polymorphism in FCER2 gene are good responders to ICS; however, asthmatic children with homozygous variant CC of rs28364072 are poorly responsive to ICS.

Social care: an essential aspect of mental health rehabilitation services.

This study is aimed at the importance of social care in rehabilitation. A brief overview of the social care theme is used as the methodology. There is a tension in mental health care between biological and psychological treatments that focus on deficits at the individual level (symptoms, disabilities) and social interventions that try to address local inequalities and barriers in order to improve access for service users to ordinary housing, employment and leisure opportunities. The history of mental health care tells us that social care is often underfunded and too easily dismissed as not the business of health care. But too much emphasis on a health model of individual deficits is a slippery slope to institutionalisation by way of therapeutic nihilism. Rehabilitation services follow the biopsychosocial model but with a shift in emphasis, recognising the vital role played by social interventions in improving the functional outcomes that matter to service users including access to housing, occupation, leisure facilities and the support of family and friends. In conclusion, rehabilitation is framed within a model of personal recovery in which the target of intervention is to boost hope and help the individual find a meaning to life, living well regardless of enduring symptoms.

Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

Virtual reality in the assessment and treatment of psychosis: a systematic review of its utility, acceptability and effectiveness.

Over the last two decades, there has been a rapid increase of studies testing the efficacy and acceptability of virtual reality in the assessment and treatment of mental health problems. This systematic review was carried out to investigate the use of virtual reality in the assessment and the treatment of psychosis. Web of Science, PsychInfo, EMBASE, Scopus, ProQuest and PubMed databases were searched, resulting in the identification of 638 articles potentially eligible for inclusion; of these, 50 studies were included in the review. The main fields of research in virtual reality and psychosis are: safety and acceptability of the technology; neurocognitive evaluation; functional capacity and performance evaluation; assessment of paranoid ideation and auditory hallucinations; and interventions. The studies reviewed indicate that virtual reality offers a valuable method of assessing the presence of symptoms in ecologically valid environments, with the potential to facilitate learning new emotional and behavioural responses. Virtual reality is a promising method to be used in the assessment of neurocognitive deficits and the study of relevant clinical symptoms. Furthermore, preliminary findings suggest that it can be applied to the delivery of cognitive rehabilitation, social skills training interventions and virtual reality-assisted therapies for psychosis. The potential benefits for enhancing treatment are highlighted. Recommendations for future research include demonstrating generalisability to real-life settings, examining potential negative effects, larger sample sizes and long-term follow-up studies. The present review has been registered in the PROSPERO register: CDR 4201507776.

Ten-year outcomes in first episode psychotic major depression patients compared with schizophrenia and bipolar patients.

We aimed to investigate long-term outcomes in psychotic major depression patients compared to schizophrenia and bipolar/manic psychosis patients, in an incidence sample, while accounting for diagnostic change. Based on Aetiology and Ethnicity in Schizophrenia and Other Psychoses (ÆSOP and ÆSOP-10), a first episode psychosis cohort was followed-up 10years after first presentation. The Schedules for Clinical Assessment in Neuropsychiatry, WHO Life Chart and Global Assessment of Functioning were used to assess clinical, social and service use outcomes. Seventy-two PMD patients, 218 schizophrenia patients and 70 psychotic bipolar disorder/mania patients were identified at baseline. Differences in outcome between PMD and bipolar patients based on baseline and lifetime diagnosis were minimal. Differences in clinical, social and service use outcomes between PMD and schizophrenia were more substantial with PMD patients showing better outcomes on most variables. However, there was some weak evidence (albeit not quite statistically significant at p<0.05) based on lifetime diagnoses that PMD patients were more likely to attempt suicide (OR 2.31, CI 0.98-5.42, p0.055) and self-harm (OR 2.34, CI 0.97-5.68, p0.060). PMD patients have better social and service use outcomes compared to people with schizophrenia, but may be more likely to attempt suicide or self-harm. This unique profile is important for clinicians to consider in any risk assessment.

Review of recent guidelines and consensus statements on hereditary angioedema therapy with focus on self-administration.

Consensus meetings and the resulting recommendations shape treatment choices in rare diseases such as hereditary angioedema (HAE) because they combine the experience of prescribing physicians and the patients who are receiving therapy. Self-administration of HAE therapy was recognised as a potential treatment option in the first consensus publication in 2003. Recent studies have confirmed that self-administration of therapy resolves attacks quickly, safely and minimises burden of disease; however, the discovery of inconsistent treatment approaches is a concern and warrants investigation into the barriers that prevent adherence with current recommendations.

Current status of implementation of self-administration training in various regions of Europe, Canada and the USA in the management of hereditary angioedema.

Results from a 16-question survey about self-administration of hereditary angioedema (HAE) therapy, administered in Europe, Canada and the USA, were used to guide discussion at an international HAE expert meeting. The aim was to capture information about current practice in self-administered HAE therapy in these countries, including self-administration training, the key benefits of switching to self-administration, the barriers to self-administration and trends in self-administration. Overall, switching to self-administration therapy is looked upon favourably from both patient and clinician perspectives by virtue of the potential improvement in quality of life arising from optimisation of therapy and early intervention. The recent changes to product licences allowing self-administration provide additional options for the management of HAE.

Update on treatment of hereditary angioedema.

Hereditary angioedema (HAE) is a rare disease characterized by recurrent, self-limiting episodes of swelling. New research and therapies have recently emerged and are now available; however, many physicians are not aware of the new developments in HAE. To update immunologists and other health care providers on new advances in HAE therapies, a PubMed, OVID and Google literature search were used to develop this manuscript. English language peer-reviewed angioedema articles were selected. High quality clinical trials were reviewed and summarized. Acute therapy in the past often consisted of symptom relief with narcotics, hydration and fresh frozen plasma (FFP). Androgens and FFP are frequently used despite multiple, significant side-effects. Newer therapies include C1-inhibitor - both human plasma derived and recombinant - as well as contact system modulators such as ecallantide and icatibant. These newer products can be used for treatment of acute attacks of HAE, and C1-inhibitors can also be used for prophylaxis. These disease-specific therapies have proven to work by placebo-controlled studies, have minimal adverse effects and can be utilized for the treatment of HAE.

C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final results of the I.M.P.A.C.T.2 study.

BACKGROUND: The placebo-controlled study International Multicentre Prospective Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1-INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. METHODS: I.M.P.A.C.T.2 was an open-label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20 U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes included patient-reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per-patient and per-attack basis. Safety assessments included adverse events, vital signs, viral safety and anti-C1-INH antibodies. RESULTS: During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per-patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39-0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8-26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti-C1-INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1-INH antibodies were detected in any patient. CONCLUSIONS: A single dose of 20 U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term treatment of successive HAE attacks at any body location.

Predicting worsening asthma control following the common cold.

The asthmatic response to the common cold is highly variable, and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multicentric cohort study of 413 adult subjects with asthma, the mini-Asthma Control Questionnaire (mini-ACQ) was used to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models were used to examine demographic, physiological, serological and cold-related characteristics for their relationship to changes in asthma control following a cold. Clinically significant worsening of asthma control was observed following a cold (mean+/-SD increase in mini-ACQ score of 0.69+/-0.93). Univariate analysis demonstrated that season, centre location, cold duration and cold severity measurements were all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed that the day 2 and cumulative sum of day 1 and 2 WURSS-21 scores were significant predictors of the subsequent changes in asthma control. In asthmatic subjects, cold severity within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold.

Variable phenotypic spectrum of diabetes mellitus in a family carrying a novel KCNJ11 gene mutation.

AIMS: Heterozygous activating mutations in KCNJ11, which encodes the Kir6.2 subunit of the pancreatic ATP-sensitive potassium (K(ATP)) channel, cause both permanent and transient neonatal diabetes. Identification of KCNJ11 mutations has important therapeutic implications, as many patients can replace insulin injections with sulphonylurea tablets. The aim was to determine if a KCNJ11 mutation was responsible for a dominantly inherited form of diabetes mellitus, showing variability in age at diagnosis, in an Italian family. METHODS: We sequenced KCNJ11 in members of a three-generation family with variable phenotypes of dominantly inherited diabetes mellitus. One had transient early-onset diabetes, one had impaired glucose tolerance during the second pregnancy, and two had young-onset diabetes. None of the subjects showed permanent neonatal diabetes or neurological symptoms. RESULTS: A novel heterozygous mutation (c. 679C-->G and c. 680A-->T) was identified, resulting in a GAG-->CTG (E227L) substitution in KCNJ11. Functional studies of recombinant heterozygous K(ATP) channels revealed a small reduction in channel inhibition by ATP (IC(50) of 15 micromol/l and 38 micromol/l for wild-type and heterozygous channels, respectively) and an increase in the resting K(ATP) current. This would be expected to impair insulin secretion. The results are in agreement with the mild phenotype of the patients. CONCLUSIONS: Our results broaden the spectrum of diabetes phenotypes resulting from KCNJ11 mutations. They indicate testing for KCNJ11 mutations should be considered not only for neonatal diabetes but also for other forms of dominantly inherited diabetes with later onset, especially where these are associated with a low body mass index and low birth weight.

Regulation of exocytosis by protein kinase C.

PKC (protein kinase C) has been known for many years to modulate regulated exocytosis in a wide variety of cell types. In neurons and neuroendocrine cells, PKC regulates several different stages of the exocytotic process, suggesting that these multiple actions of PKC are mediated by phosphorylation of distinct protein targets. In recent years, a variety of exocytotic proteins have been identified as PKC substrates, the best characterized of which are SNAP-25 (25 kDa synaptosome-associated protein) and Munc18. In the present study, we review recent evidence suggesting that site-specific phosphorylation of SNAP-25 and Munc18 by PKC regulates distinct stages of exocytosis.

Efficacy of the topical nasal steroid budesonide on improving sleep and daytime somnolence in patients with perennial allergic rhinitis.

BACKGROUND: Improving quality of life is considered to be a major endpoint and motivation for clinical intervention in patients with perennial allergic rhinitis (PAR). In addition to classical symptoms of congestion, pruritus, and rhinorrhea, patients will often complain of not being able to sleep well at night and of feeling fatigued during the day. Like sleep apnea, PAR has also been shown to cause sleep disturbance and consequently worsen daytime fatigue and somnolence. HYPOTHESIS: It is proposed that by decreasing nasal obstruction due to allergic rhinitis by treating with the topical steroid budesonide, symptoms of daytime fatigue and somnolence can be improved. METHODS: Twenty-two subjects were enrolled in a double-blind, placebo-controlled, crossover study using Baalam's design. Patients were treated with either budesonide 128 g/day or placebo. Subjective data include the Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Rhino-conjunctivitis Quality of Life Questionnaire, and a daily diary recording nasal symptoms, sleep problems, and daytime fatigue. RESULTS: The results illustrated that the topical nasal corticosteroid significantly improved daytime fatigue (P = 0.03), somnolence (P = 0.02), and quality of sleep (P = 0.05) compared to placebo in patients suffering from PAR. SUMMARY: Budesonide is able to improve congestion, sleep, and daytime somnolence.

CheR- and CheB-dependent chemosensory adaptation system of Rhodobacter sphaeroides.

Rhodobacter sphaeroides has multiple homologues of most of the Escherichia coli chemotaxis genes, organized in three major operons and other, unlinked, loci. These include cheA(1) and cheR(1) (che Op(1)) and cheA(2), cheR(2), and cheB(1) (che Op(2)). In-frame deletions of these cheR and cheB homologues were constructed and the chemosensory behaviour of the resultant mutants examined on swarm plates and in tethered cell assays. Under the conditions tested, CheR(2) and CheB(1) were essential for normal chemotaxis, whereas CheR(1) was not. cheR(2) and cheB(1), but not cheR(1), were also able to complement the equivalent E. coli mutants. However, none of the proteins were required for the correct polar localization of the chemoreceptor McpG in R. sphaeroides. In E. coli, CheR binds to the NWETF motif on the high-abundance receptors, allowing methylation of both high- and low-abundance receptors. This motif is not contained on any R. sphaeroides chemoreceptors thus far identified, although 2 of the 13 putative chemoreceptors, McpA and TlpT, do have similar sequences. This suggests that CheR(2) either interacts with the NWETF motif of E. coli methyl-accepting chemotaxis proteins (MCPs), even though its native motif may be slightly different, or with another conserved region of the MCPs. Methanol release measurements show that R. sphaeroides has an adaptation system that is different from that of Bacillus subtilis and E. coli, with methanol release measurable on the addition of attractant but not on its removal. Intriguingly, CheA(2), but not CheA(1), is able to phosphorylate CheB(1), suggesting that signaling through CheA(1) cannot initiate feedback receptor adaptation via CheB(1)-P.

Developmental and regional distribution of aspartoacylase in rat brain tissue.

The function of N-acetyl-aspartate (NAA), a predominant molecule in the brain, has not yet been determined. However, NAA is commonly used as a putative marker of viable neurones. To investigate the possible function of NAA, we determined the anatomical, developmental and cellular distribution of aspartoacylase, which catalyses the hydrolysis of NAA. Levels of aspartoacylase activity were measured during postnatal development in several brain regions. The differential distribution of aspartoacylase activity in purified populations of cells derived from the rat CNS was also investigated. The developmental and anatomical distribution of aspartoacylase correlated with the maturation of white matter tracts in the rat brain. Activity increased markedly after 7 days and coincided with the time course for the onset of myelination in the rat brain. Gray matter showed little activity or developmental trend. There was a 60-fold excess in optic nerve (a white matter tract) when compared with cortex at 21 days of development. In the adult brain there was a 18-fold difference in corpus callosum compared with cortex (stripped of corpus callosum). Cellular studies demonstrated that purified cortical neurons and cerebellar granular neurones have no activity. Primary O-2A progenitor cells had moderate activity, with three-fold higher activity in immature oligodendrocyte and 13-fold increase in mature oligodendrocytes (myelinating cells of the CNS). The highest activity was seen in type-2 astrocytes (20-fold difference compared with O-2A progenitors) derived from the same source. Aspartoacylase activity increased with time in freshly isolated astrocytes, with significantly higher activity after 15 days in culture. We conclude that aspartoacylase activity in the developing postnatal brain corresponds with maturation of myelination, and that the cellular distribution is limited to glial cells.

Dual components of optimal asthma therapy: scientific and clinical rationale for the use of long-acting beta-agonists with inhaled corticosteroids.

The authors describe the scientific rationale for using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. They discuss the clinical trials demonstrating that using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist provides greater overall asthma control compared with increasing the dose of inhaled corticosteroid. In addition, they review the clinical trials comparing the addition of a leukotriene modifier to an inhaled corticosteroid versus using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. Discussion also includes descriptions of trials showing reduced exacerbations of asthma when using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist. Finally, the authors provide evidence for the ability to detect deteriorating asthma when using an inhaled corticosteroid with an inhaled long-acting beta 2-agonist, and they provide a comparison of salmeterol and formoterol, two long-acting beta 2-agonists.

A retrospective study of risk factors for repeated admissions for asthma in a rural/suburban university hospital.

In the study reported, the authors examined risk factors for repeated hospital admissions for asthma in a rural/suburban setting. Charts of patients who were hospitalized two or more times with the diagnosis of asthma between June 1991 and January 1998 were reviewed. A questionnaire was completed for each admission for 65 patients. The results demonstrated an equal male-to-female ratio, with a mean age of 27 years. Hispanics represented 12% of the patients although they accounted for only 2.5% of the general population in the area under study. The mean number of hospital admissions was 3.2. A history of depression existed in 25% of the patients. Noncompliance was admitted in 38%. Twenty-five percent were active tobacco smokers. Acknowledged triggers of asthma included viral infections (74%), exercise (50%), weather conditions (43%), dust (38%), cats (36%), sinusitis (32%), pollen (32%), gastroesophageal reflux disease (31%), dogs (30%), smoke (28%), and emotional stress (15%). Medications at time of admission included albuterol (98%), salmeterol xinafoate (26%), theophylline (38%), ipratropium bromide (55%), nedocromil sodium (20%), cromolyn sodium (35%), prednisone (49%), and inhaled corticosteroids (69%). Ninety-five percent had access to a primary care physician. Fifty-seven percent had a pulmonary and 11% had an allergy consult. These data suggest that patients in rural/suburban areas with repeated hospitalizations for asthma have a high probability of noncompliance, depression, and allergenic triggers. Gastroesophageal reflux was a common recognized trigger. Inhaled steroids were underused, whereas ipratropium and theophylline were overused. Bilingual education on asthma and triggers and social support are necessary even in rural healthcare settings without a large minority population.

Allergy test results of a rural and small-city population compared with those of an urban population.

The frequency of sensitization to environmental antigens changes in different regions. As such, the pattern of sensitivity to common allergens was studied at multiple sites across central Pennsylvania, an area composed of small cities and rural communities, to determine uniqueness of allergies in populations from this area in contrast to allergies as determined by skin testing in large urban centers. The study reported was undertaken to determine allergen variation from an urban population compared with a rural population of a Northeastern state so that environmental avoidance and immunotherapy can be more precisely prescribed. Patient charts were retrospectively reviewed to determine sensitivity to house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cockroach, Penicillium, Aspergillus spp, dog, cat, timothy grass, ragweed, oak, and Alternaria tenuis at five sites in Pennsylvania. All of these sites were classified as "small city" or "rural" for the study. One hundred patient records were examined at each site for the results of allergy testing by the prick puncture, radioallergosorbent test (RAST), or intradermal methods. These small-city and rural data were pooled and compared with that of the National Cooperative Inner-City Asthma Study (NCI-CAS), which included 1286 patients from urban environments. The prevalence of allergy to both species of dust mites, dog, timothy grass, and ragweed was significantly greater in the pooled rural group than in the NCICAS inner-city patients (P < .05). In contrast, sensitivity to cockroach antigens and Alternaria was significantly greater in the NCICAS urban population than in the pooled rural group (P < .05). No statistically significant difference was found between the NCICAS and the pooled rural patients in reference to Penicillium, cat, and oak (P > .05).

Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study.

The safety of sputum induction and the reproducibility of measurements in induced sputum in multicenter studies is unknown. We examined the safety of sputum induction in a two-visit, six-center study in 79 subjects with moderate to severe asthma (mean +/- SD FEV(1) 71 +/- 12% predicted, 67% taking inhaled corticosteroids). In addition, we compared the reproducibility of markers of inflammation in induced sputum with the reproducibility of the FEV(1) and the methacholine PC(20). The FEV(1) decreased > or = 20% from the postbronchodilator baseline in 14% of all subjects and in 25% of subjects whose initial prebronchodilator baseline was 40 to 60% of predicted. All subjects responded promptly to additional albuterol treatment, and no subject developed refractory bronchoconstriction requiring treatment other than reversal of bronchospasm in the study laboratory. The reproducibility of measurements of the eosinophil percentage, eosinophil cationic protein, tryptase, and methacholine PC(20) were similar (concordance correlation coefficients of 0.74, 0.81, 0.79, and 0.74, respectively), without any significant among-center effect. We conclude that sputum induction can be performed safely in subjects with moderate to severe asthma in multicenter clinical trials when carried out under carefully monitored conditions. Importantly, we demonstrate that measurement of markers of inflammation in induced sputum is as reproducible as methacholine PC(20) and should prove useful in the assessment of airway inflammation in multicenter clinical trials.