An unusual case of alpha-1-antitrypsin deficiency: SZ/Z.

A female patient was first seen at age 65 due to a diagnosis of alpha-1-antitrypsin deficiency (AATD). She was a lifelong non-smoker, with no significant history of second hand smoke exposure. There was no prior family history of AATD or liver disease. Her serum AAT concentration was measured on two occasions and in both cases, concentration was <0.21 g/L. The patient was referred for genetic testing to determine her SERPINA1 (the gene responsible for AATD) genotype. Three deficiency alleles were identified: she was heterozygous for S, a mild deficiency allele, and homozygous for Z, a severe deficiency allele. This case represents unusual convergence of three pathogenic SERPINA1 variants in a single individual. We report the investigations used to clarify her unusual genotype and propose non-crossover gene conversion as the likely mechanism.

Characteristics of COPD in never-smokers and ever-smokers in the general population: results from the CanCOLD study.

BACKGROUND: There is limited data on the risk factors and phenotypical characteristics associated with spirometrically confirmed COPD in never-smokers in the general population. AIMS: To compare the characteristics associated with COPD by gender and by severity of airway obstruction in never-smokers and in ever-smokers. METHOD: We analysed the data from 5176 adults aged 40 years and older who participated in the initial cross-sectional phase of the population-based, prospective, multisite Canadian Cohort of Obstructive Lung Disease study. Never-smokers were defined as those with a lifetime exposure of <1/20 pack year. Logistic regressions were constructed to evaluate associations for 'mild' and 'moderate-severe' COPD defined by FEV1/FVC <5th centile (lower limits of normal). Analyses were performed using SAS V.9.1 (SAS Institute, Cary, North Carolina, USA). RESULTS: The prevalence of COPD (FEV1/FVC

Exacerbation-like respiratory symptoms in individuals without chronic obstructive pulmonary disease: results from a population-based study.

RATIONALE: Exacerbations of COPD are defined clinically by worsening of chronic respiratory symptoms. Chronic respiratory symptoms are common in the general population. There are no data on the frequency of exacerbation-like events in individuals without spirometric evidence of COPD. AIMS: To determine the occurrence of 'exacerbation-like' events in individuals without airflow limitation, their associated risk factors, healthcare utilisation and social impacts. METHOD: We analysed the cross-sectional data from 5176 people aged 40 years and older who participated in a multisite, population-based study on lung health. The study cohort was stratified into spirometrically defined COPD (post-bronchodilator FEV1/FVC < 0.7) and non-COPD (post bronchodilator FEV1/FVC ≥ 0.7 and without self-reported doctor diagnosis of airway diseases) subgroups and then into those with and without respiratory 'exacerbation-like' events in the past year. RESULTS: Individuals without COPD had half the frequency of 'exacerbation-like' events compared with those with COPD. In the non-COPD group, the independent associations with 'exacerbations' included female gender, presence of wheezing, the use of respiratory medications and self-perceived poor health. In the non-COPD group, those with exacerbations were more likely than those without exacerbations to have poorer health-related quality of life (12-item Short-Form Health Survey), miss social activities (58.5% vs 18.8%), miss work for income (41.5% vs 17.3%) and miss housework (55.6% vs 16.5%), p<0.01 to <0.0001. CONCLUSIONS: Events similar to exacerbations of COPD can occur in individuals without COPD or asthma and are associated with significant health and socioeconomic outcomes. They increase the respiratory burden in the community and may contribute to the false-positive diagnosis of asthma or COPD.

Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline.

Alpha-1 antitrypsin (A1AT) functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD). Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted) attributable to emphysema and documented A1AT deficiency (level ≤11 µmol/L) who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation) because of benefits in computed tomography scan lung density and mortality.

The clinical impact of single inhaler therapy in asthma.

BACKGROUND: Low-dose budesonide/formoterol combination used in the SMART fashion with symptom-reactive supplemental dosing has been reported to reduce asthma exacerbations as compared to the use of budesonide alone or to lower doses of budesonide/formoterol without supplemental dosing. OBJECTIVE: We undertook to review the non-exacerbation outcomes of SMART therapy and to assess the patient education implications of this treatment strategy. MATERIALS & METHODS: Systematic review. RESULTS: Patients treated with this strategy appear to be under-treated in that the majority fail to achieve guideline-defined control standards. The SMART strategy has not been tested against equivalent or higher doses of budesonide/formoterol given in symptom-prevention fashion. Existing educational strategies that focus on recognition of poor disease control may not be applicable with SMART therapy and the use of action plans has not been clarified with this symptom-reactive strategy. There is some evidence from that the current clinical use of SMART therapy may be contaminated frequently by the concurrent prescription of short-acting bronchodilators. There is no information on long-term outcomes with a symptom-reactive ICS/LABA strategy but the use of the strategy for one year has been associated with rising sputum and airway biopsy eosinophil counts. CONCLUSION: Despite fewer severe exacerbations with SMART therapy as compared to ICS monotherapy or lower dose ICS/LABA therapy, the strategy produces poor day-to-day control of symptoms and is associated with increasing inflammation. CLINICAL RELEVANCE: The symptom-reactive strategy described as SMART therapy is associated with poor symptom control of asthma.

A 21-year-old man with systemic-onset juvenile rheumatoid arthritis, cough and progressive dyspnea.

Primary or nonobstructive, endogenous lipoid pneumonia is a rare clinical entity usually associated with an underlying systemic disease. The present report describes a case involving a 21-year-old man with systemic-onset juvenile rheumatoid arthritis who developed primary endogenous lipoid pneumonia. Multiple treatment regimens were attempted; however, definitive management was only achieved through double-lung transplantation.

Diagnosis and treatment considerations for women with COPD.

The worldwide prevalence of chronic obstructive pulmonary disease (COPD) is growing faster in women than in men. Over the past two decades, COPD-related mortality rates have also grown faster in women, and since the year 2000 more women than men have died from COPD. The greater prevalence of COPD and related mortality reported for men in earlier epidemiological studies may be due to under-diagnosis of women. In addition, factors such as prevalence of symptoms, triggering stimuli, response to treatment, susceptibility to smoking, frequency of exacerbations, impairment in quality of life response to oxygen therapy, presence of malnutrition, airway hyper-responsiveness and depression are more frequently seen in women with COPD. Despite these differences, the current guidelines for the diagnosis and treatment of men or women with COPD are the same. It is important for healthcare professionals to recognise the gender differences in patients with COPD to optimise assessment, monitoring and treatment of this disease. This article reviews the clinical differences between men and women with COPD, current treatment guidelines and its implications for improvement in the management of women with COPD.

Suboptimal asthma control: prevalence, detection and consequences in general practice.

Telephone surveys describing suboptimal asthma control may be biased by low response rates. In order to obtain an unbiased assessment of asthma control and assess its impact in primary care, primary care physicians used a 1-page control questionnaire in 50 consecutive asthma patients. Of the 10,428 patients assessed by 354 physicians, 59% were uncontrolled, 19% well-controlled and 23% totally controlled. Physicians overestimated control, regarding only 42% of patients as uncontrolled. Physicians were more likely to report plans to alter the regimens of uncontrolled patients than controlled patients (1.29 versus 0.20 medication changes per patient) doing so in a fashion consistent with guideline recommendations. Of the uncontrolled patients, 59% required one or more urgent care or specialist visits versus 26 and 15% of well-controlled or totally controlled patients, respectively. Patients were more likely to report short-term symptom control when they had not required urgent or specialist care (odds ratio 5.68; 95% confidence interval 4.91-6.58). The majority of asthma patients treated in general practice are uncontrolled. Lack of control can be recognised by physicians who are likely to consider appropriate changes to therapy. A lack of short-term symptom control of asthma is associated with excess healthcare utilisation.

[Attitudes toward the diagnosis of chronic obstructive pulmonary disease in primary care]. / Problemas con el diagnóstico de la EPOC en atención primaria.

OBJECTIVE: Although the prevalence of chronic obstructive pulmonary disease (COPD) has increased among women, it is still considered a disease that mainly affects men. This study aimed to identify the diagnostic attitudes of primary care physicians toward patients with COPD according to gender and spirometric results. METHODS: A representative sample of 839 primary care physicians participated in the study. Each physician dealt with 1 of 8 hypothetical cases based on a patient diagnosed with COPD. In half the cases, the physician was told the patient was a man. The other half of the physicians were told the same patient was a woman. After presentation of the medical history and results of physical examination, the physicians were asked to state a probable diagnosis and indicate the diagnostic tests that were necessary. They were then told the results of spirometry, which indicated obstruction ranging from moderate to severe. Negative results of bronchodilator tests and oral corticosteroid tests were then communicated. RESULTS: COPD was more likely to be the preliminary diagnosis for male patients than for females (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.15-2.1). This gender bias disappeared once the physicians were shown the abnormal results of spirometry. Patients with severe obstruction were more likely to be diagnosed with COPD than those with moderate obstruction (OR, 1.5; 95% CI, 1.08-2.09). CONCLUSIONS: There is gender bias in the diagnosis of COPD. Patients with moderate obstruction are often believed not to have COPD. These biases may compromise the early diagnosis of the disease in a group of patients with ever increasing risk.

Problemas con el diagnóstico de la EPOC en atención primaria / Attitudes toward the diagnosis of Chronic Obstructive Pulmonary Disease in primary care

Objetivo: La prevalencia de la enfermedad pulmonar obstructiva crónica (EPOC) ha aumentado en el sexo femenino, pero aún se considera una enfermedad que afecta sobre todo a los varones. Este estudio pretendió identificar las actitudes diagnósticas de los médicos de atención primaria frente a pacientes con EPOC según su sexo y los resultados de la espirometría. Método: Participó en el estudio una muestra representativa de 839 médicos de atención primaria. Cada uno de ellos resolvió uno entre 8 casos posibles de pacientes con EPOC. La mitad de éstos correspondía a un paciente varón y la otra mitad a una mujer con historia clínica y exploración física idénticas. Tras la historia y la exploración física se solicitó a los participantes un diagnóstico provisional, así como las pruebas diagnósticas necesarias. Se facilitaron después los resultados de la espirometría que mostraban una obstrucción de carácter moderado o grave. Los resultados negativos de una prueba broncodilatadora y de una prueba con corticoides orales se dieron a continuación. Resultados: La EPOC fue un diagnóstico provisional más probable para los pacientes varones que para las mujeres (odds ratio [OR]: 1,55; intervalo de confianza [IC] del 95%, 1,15-2,1). Este sesgo desaparecía después de mostrar los resultados anormales de la espirometría. Los pacientes con una obstrucción de carácter grave eran diagnosticados con mayor probabilidad de EPOC que aquellos con una obstrucción moderada OR: 1,5; IC del 95%, 1,08-2,09). Conclusiones: Existe un sesgo diagnóstico en función del sexo del paciente. En muchas ocasiones no se diagnostica a los pacientes con EPOC que presentan una obstrucción moderada. Estos sesgos podrían comprometer el diagnóstico precoz de la EPOC en un grupo cada vez más frecuente de individuos en riesgo

Objective: Although the prevalence of chronic obstructive pulmonary disease (COPD) has increased among women, it is still considered a disease that mainly affects men. This study aimed to identify the diagnostic attitudes of primary care physicians toward patients with COPD according to gender and spirometric results. Methods: A representative sample of 839 primary care physicians participated in the study. Each physician dealt with 1 of 8 hypothetical cases based on a patient diagnosed with COPD. In half the cases, the physician was told the patient was a man. The other half of the physicians were told the same patient was a woman. After presentation of the medical history and results of physical examination, the physicians were asked to state a probable diagnosis and indicate the diagnostic tests that were necessary. They were then told the results of spirometry, which indicated obstruction ranging from moderate to severe. Negative results of bronchodilator tests and oral corticosteroid tests were then communicated. Results: COPD was more likely to be the preliminary diagnosis for male patients than for females (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.15-2.1). This gender bias disappeared once the physicians were shown the abnormal results of spirometry. Patients with severe obstruction were more likely to be diagnosed with COPD than those with moderate obstruction (OR, 1.5; 95% CI, 1.08-2.09). Conclusions: There is gender bias in the diagnosis of COPD. Patients with moderate obstruction are often believed not to have COPD. These biases may compromise the early diagnosis of the disease in a group of patients with ever increasing risk

Impact of 'mild' asthma on health outcomes: findings of a systematic search of the literature.

The present bibliographic review shows that patients considered to have mild asthma often suffer impairment in quality of life (QoL) and use considerable scheduled and unscheduled health care resources. I found that asthma investigators used no consistent classification scheme for asthma severity, and the level of agreement amongst specialists when categorizing patients with asthma was low. Asthma severity has been classified using a wide range of parameters including medication use, asthma symptoms, lung function, hospitalizations and incidence of exacerbations. Most studies showed a general association between asthma severity and health-related quality of life (HRQoL) such that patients with severe disease suffered greater impairment. However, few patients with mild asthma enjoyed unimpaired HRQoL. Indeed depression and impaired HRQoL were reported as frequently in patients with mild asthma as in those with more severe disease. Although in general severe patients used the most health care resources, even patients with mild asthma used considerable health care resources including emergency room care and hospitalizations. In summary, the term 'mild' when applied to asthma is potentially misleading given the impaired HRQoL and avoidable health care utilization prevalent amongst such patients. The application of disease severity classification in clinical asthma management has not been validated. It may now be appropriate to examine these classifications more critically in order to determine if they have clinical or research usefulness. By contrast, the strategy of treating to achieve disease control has been validated and offers the advantage of simplicity in its application.

Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma.

BACKGROUND: Inhaled corticosteroids (ICS) are recommended therapy for persistent asthma, although side effects can limit appropriate use. Ciclesonide, a novel ICS, is activated in the lung, thereby reducing systemic activity and side effects. This 12-week, double-blind, randomized, parallel-group, placebo-controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma. METHODS: After a 2-week baseline period in which current ICS treatment was continued, 329 patients were randomized to receive ciclesonide 160 microg (n = 107) or 640 microg (n = 112) (ex-actuator doses, equivalent to 200 and 800 microg ex-valve, respectively), or placebo (n = 110) once daily in the morning. Efficacy was monitored by asthma symptom scores, rescue medication use, morning and evening peak expiratory flow (PEF) measurements, spirometry, and probability of study completion without experiencing lack of efficacy. RESULTS: Morning PEF remained stable with either ciclesonide dose but decreased with placebo; the differences were significant (P < 0.0001) for both ciclesonide doses vs placebo. The forced expiratory volume in 1 s and forced vital capacity decreased significantly with placebo (P < 0.005), but were unchanged with ciclesonide. Lack of efficacy was significantly greater for patients switched to placebo (63%) than it was for those treated with ciclesonide 160 microg (30%) (P < 0.0001 vs placebo) or ciclesonide 640 microg (31%) (P < 0.0001 vs placebo). There were no significant differences between the two tested doses of ciclesonide with respect to efficacy and safety. Serum and 24-h urine cortisol were unaffected by ciclesonide treatment. Both doses of ciclesonide were well tolerated with no cases of oral candidiasis. CONCLUSION: Ciclesonide (160 or 640 microg) once daily in the morning effectively maintains asthma control, does not affect cortisol levels, and has an adverse event profile comparable with placebo in adults with primarily mild to moderate asthma.

The burden of COPD in Canada: results from the Confronting COPD survey.

Chronic obstructive pulmonary disease (COPD) is a condition characterized by progressive airflow limitation, with symptoms of dyspnoea, cough, and sputum production. Aside from information on prevalence, mortality and hospital resource utilization arising from COPD in Canada, there is a lack of data on the impact of the disease on primary care healthcare resource utilization and the economic burden of the disease (i.e. direct and indirect costs). Canada is not unusual in this respect, as surprisingly few studies have attempted to quantify the impact of COPD on the healthcare system and society in other countries. In an attempt to address the need for information on the burden of COPD, an economic analysis of data from a large-scale international survey, Confronting COPD in North America and Europe, was conducted in Canada and six other countries. The results of the Canadian survey estimated the direct cost of the disease at CA dollar 1997.81 per patient, with over half of this due to inpatient hospitalizations. COPD also had an impact on the economy, with indirect costs amounting to CA dollar 1198.18, a third of the total per patient cost of COPD to society (CA dollar 3195.97). Reducing the impact of this disease will necessitate improvements to the way the disease is managed in primary care, as poor symptom control and frequent exacerbations are key drivers of hospital and other unscheduled care costs. Early diagnosis and the application of available but underused interventions (e.g. smoking cessation, inhaled drug therapies and pulmonary rehabilitation) could reduce the morbidity and costs of COPD in this country.

Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review.

OBJECTIVE: To determine whether systemic corticosteroids are of benefit to patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: An English-language search of MEDLINE (1966 to February 2002) and the Cochrane Library and a bibliographic review was performed to identify published clinical trials of systemic corticosteroid administration in acute exacerbations of COPD. All relevant English-language, randomized, placebo-controlled clinical trials were considered. Trials investigating the adverse effects of systemic steroids were also retrieved. Studies were assigned a quality rating according to explicit criteria. Clinically relevant end points, such as treatment failure and duration of hospital stay, were considered preferentially. To compare outcomes across all qualifying studies, we considered the difference in spirometric measures between treatment and placebo groups. Potential confounding factors and bias relating to patient selection, treatment protocols, and outcome measurement were considered independently for each study. RESULTS: Among the 8 studies that met all criteria, 5 found that significant improvement in forced expiratory volume in 1 second (>20%) was associated with steroid administration. Two studies found improvement in clinically relevant outcomes. One published study and 2 study abstracts did not find significant improvement in spirometric measures with corticosteroid administration. CONCLUSION: Short courses of systemic corticosteroids in acute exacerbations of COPD have been shown to improve spirometric outcomes (good-quality evidence) and clinical outcomes (good-quality evidence).

Indirect effects of heavy metals on parasites may cause shifts in snail species compositions.

We studied the direct and indirect effects of pollution on the distributions and abundances of two closely related species of pulmonate freshwater snails. Physella columbiana is more numerous at heavy metal-polluted lakes, and Lymnaea palustris is more numerous at reference lakes. Both species are present at all sites, as are predatory bluegill sunfish (Lepomis macrochirus). The direct effects examined included the snails' growth and reproduction in both the presence and absence of heavy metals and their short-term survival when exposed to large concentrations of heavy metals. The indirect effects were the species' ability to elude capture by sunfish and the diversity and abundance of parasites within the snails. We found that heavy metals had little direct effect on growth and reproduction and that both species acquired similar levels of metals in their tissues. Interestingly, P. columbiana (the more abundant species in polluted lakes) actually exhibited higher recruitment in the absence of metals than did L. palustris (reference lakes). L. palustris has life history characteristics that favor increased growth and reduced reproduction. These characteristics resulted in decreased predation of adults by gape-limited predators and a greater ability to cope with heavy parasite burdens. P. columbiana exhibited slower growth, which resulted in increased predation although higher reproduction rates may compensate.The major effect of heavy metals on species distributions was indirect on the snails' parasites. Parasites appeared to be very susceptible to metals, and this resulted in lower parasite diversity and intensities at polluted sites for both species of snails. P. columbiana may only be able to outcompete L. palustris at polluted sites due to the indirect effects of heavy metals; the negative effect of heavy metals on parasites, and a proposed negative effect of metals on the foraging ability of sunfish that favors the faster-reproducing P. columbiana.

Inhaled beclomethasone dipropionate improves acoustic measures of voice in patients with asthma.

BACKGROUND: Inhaled corticosteroids have the potential to produce upper-airway side effects such as hoarseness. As new compounds and delivery devices are developed and compared, it is difficult to quantify their adverse upper-airway effects. OBJECTIVE: We undertook the following study to test the ability of an acoustic analysis technique to quantify changes in vocal function in steroid-naive patients with asthma who receive inhaled beclomethasone dipropionate (BDP), 1,000 microg/d for 4 months. METHODS: Patients self-administered one of four regimens of inhaled BDP. Group 1 patients received one 250-microg puff qid via metered-dose inhaler (MDI); group 2 patients received one 250-microg puff qid via MDI with a holding chamber; group 3 patients received two 250-microg puffs bid via MDI; and group 4 patients received two 250-microg puffs bid via MDI with a holding chamber. A smaller cohort of nonsmoking asthmatic patients was managed without steroid intervention for 4 months. At baseline and again at 8 weeks and 16 weeks after the initiation of BDP treatment, patients underwent spirometry and methacholine challenge. At baseline and again at 2, 4, 8, 12, and 16 weeks, patients underwent voice recording for analysis of voice parameters. The recorded vowels were low-pass filtered (10 KHz), digitized (22 KHz), and analyzed by software to obtain two acoustic measures: (1) jitter, the cycle-to-cycle variation in the time period of the voice signal; and (2) shimmer, the cycle-to-cycle variation in voice signal amplitude. RESULTS: We recruited 77 patients for randomization to inhaled steroid therapy and 10 patients who continued to receive only occasional inhaled bronchodilator therapy. In all active treatment groups, FEV(1), FVC, and provocative concentration of methacholine causing a 20% fall in FEV(1) improved significantly after BDP treatment. Mean jitter scores, a measurement of variation in voice pitch, were not significantly influenced by BDP treatment. However, mean shimmer scores, a reflection of perturbation in vocal amplitude, fell significantly (p < 0.05) in the active treatment groups. These reductions in shimmer scores were not significantly different in the active treatment groups. Shimmer scores in the bronchodilator-treated group were unchanged during the 16 weeks of follow-up. CONCLUSIONS: Our data show that a simple and noninvasive acoustic analysis of voice is sensitive to subclinical changes associated with inhaled corticosteroid therapy. We have shown that 1,000 microg/d of inhaled BDP actually improves specific acoustic measures of voice in patients with inadequately controlled asthma. These improvements were uninfluenced by dosing schedule and whether a spacing chamber was used.

Patient handling of a dry-powder inhaler in clinical practice.

BACKGROUND: Multi-dose dry-powder inhalers are perceived as being easier for patients to use than conventional pressurized aerosol inhalers; however, no study has determined whether patients handle such devices adequately and whether there is a need for patient education in this area. METHOD: We used trained observers to assess the handling of a specific multi-dose dry powder inhaler (Turbuhaler; AstraZeneca Canada; Mississauga, ON) by patients currently using the device for the management of their asthma. Fourteen discrete steps were scored independently by two observers simultaneously. Patients were divided into two groups for analysis: those who had received formal instruction in the use of the inhaler at The Asthma Centre and those who had received no formal instruction in the community. RESULTS: There was no significant difference between the formally trained groups and control groups in the percentage of handling steps performed correctly (79% vs 78%, respectively; p > 0.05). Fewer than 50% of patients in both groups demonstrated optimal breath-holding when using the device. CONCLUSION: Patient handling of Turbuhaler was generally good, with no evidence that a structured education intervention offered an advantage over the usual education incidental to the prescribing or dispensing process. The most common handling flaw, suboptimal breath-holding, is not specific to this device and is of uncertain clinical significance.

Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone.

There is controversy about the role of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). Although they appear to have little impact on airways obstruction or its progression, their use may reduce the frequency and/or severity of exacerbations in a subset of patients. We undertook the following study to determine the impact of inhaled corticosteroid on two noninvasive markers of airways inflammation. We assigned 20 stable nonsmoking patients with COPD in random, double-blind crossover fashion to two 2-wk treatment periods with inhaled beclomethasone 500 microg twice daily or matching placebo, followed by a 2-wk washout period. We measured exhaled nitric oxide (ENO), breath condensate H(2)O(2), and flow volume spirometry at weekly intervals. Median baseline ENO was 26.2 (19.3 to 54.8) ppb and fell significantly following 1 and 2 wk of beclomethasone (-10.6 ppb, p = 0.002, and -6.3 ppb, p = 0.013, respectively) but was unchanged by placebo inhalation. Breath condensate H(2)O(2) levels did not change significantly with inhaled beclomethasone or placebo. Although there were no significant changes in FEV(1) with BDP therapy, there was a moderate inverse correlation between changes in ENO and changes in FEV(1) (r -0.50). We conclude that inhaled beclomethasone reduces ENO levels in stable nonsmoking patients with COPD, a finding compatible with an antiinflammatory mechanism of action.

Thoracic duct cyst presenting as a left supraclavicular mass.

Thoracic duct cysts may occur either in the mediastinum or in the neck. The majority of such lesions occurring in the neck consist of chylous fistulae and are secondary to surgery on the neck. Fewer than five cases have been reported in the literature of primary thoracic duct cysts occurring in the neck (1).