C-reactive protein levels and survival in patients with moderate to very severe COPD

BACKGROUND: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease. OBJECTIVE: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease. METHODS: In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality. RESULTS: During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival. CONCLUSIONS: In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV(1), IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.     

Targeting airway inflammation in asthma: current and future therapies

Asthma is a chronic inflammatory disease of the airway that requires long-term antiinflammatory therapy. Inhaled corticosteroids (ICSs) are recommended for first-line treatment of persistent disease, but not all patients achieve asthma control even when these agents are used in high doses and in combination with other medications, including a long-acting beta(2)-agonist or a leukotriene modifier. Such patients may require additional therapy. As information about asthma pathophysiology and inflammatory phenotypes continues to increase, and additional antiinflammatory options become available, it may be possible to target antiinflammatory therapy to various aspects of the disease and consequently to improve the treatment of patients with inadequate responses to standard ICS-based therapy. Several novel antiinflammatory therapies are in different stages of clinical development. The most clinically advanced of these is omalizumab, a recombinant humanized monoclonal antibody that specifically targets IgE and is indicated for patients with moderate-to-severe asthma caused by allergies. Omalizumab has demonstrated efficacy in patients with moderate-to-severe asthma and documented evidence of allergen sensitivity. Other key therapy options in clinical development either target proinflammatory cytokines (eg, interleukin-4 and tumor necrosis factor-alpha) or inflammatory cells (eg, T-helper type 2 cells and eosinophils). This review provides an overview of the current and future approaches targeting airway inflammation in patients with asthma.     

Surfactant in airway disease

Beta(2)-adrenergic agonists cause a release of pulmonary surfactant into lung airways. The surfactant phospholipids maintain the patency of the conducting airways, but this function is inhibited by plasma proteins entering an inflamed airway. The physical behavior of the surfactant can be studied with a pulsating bubble surfactometer and a capillary surfactometer. Calf lung surfactant extract was found to be inhibited by plasma proteins and by a lowering of temperature. Severe breathing difficulties and malfunctioning surfactant developed in BALB/c mice inhaling ozone or infected with respiratory syncytial virus, mainly as a result of proteins invading the airways. Patients with asthma were challenged with allergens in an area of one lung. BAL fluid (BALF) from such an area contained a surfactant that functioned poorly (ie, an inability to maintain airway openness) compared with BALF from the other lung or from the lungs of healthy volunteers. When proteins in the BALF were removed, surfactant performance clearly improved. Eosinophils, so prominent in asthmatic patients, synthesize the enzyme lysophospholipase, which, together with the enzyme phospholipase A(2), catalyzes the hydrolysis of the main component of the surfactant, phosphatidylcholine. Such hydrolysis incapacitates the ability of the surfactant to maintain airway patency. The treatment of asthma with beta(2)-adrenergic agonists and steroids will have a valuable effect on the surfactant system. It will cause a release of fresh surfactant into terminal airways. Surfactant can also be nebulized and inhaled, which has been shown to be an effective treatment.     

Occupational asthma and work-exacerbated asthma: factors associated with time to diagnostic steps

BACKGROUND: Little is known regarding the factors associated with the times for patients' first physician visit, the first physician suspicion of work-related asthma (WRA), and final diagnosis after the onset of WRA symptoms. This study examined individual and work-related factors that are associated with longer times to these diagnostic milestones among groups with occupational asthma (OA) and work-exacerbated asthma (WEA). METHOD: Suspected WRA cases were identified from an occupational lung disease clinic and claimants to the Ontario Workplace Safety and Insurance Board (100 patients each). Questionnaire administration and chart review were undertaken. RESULTS: Eighty participants were classified as having sensitizer-induced OA and 87 as having WEA. For the OA group, the risk factors for delay included male sex, being unmarried, low education, and lack of awareness of association of symptoms with work. Other factors included older age, being the sole income earner, and lack of knowledge of the Workplace Hazardous Materials Information System program. For WEA, lower household income, lower education, absence of a health-and-safety program at work, absence of a union, and lack of awareness of OA and of agents at work that could affect asthma significantly increased the time to diagnostic milestones. CONCLUSIONS: Different factors affect the diagnostic milestones for OA and WEA. Findings suggest a need for educational programs for workers who are at risk of OA and WEA and a need for further primary care physician education on WRA.     

Paternal asthma, mold exposure, and increased airway responsiveness among children with asthma in Costa Rica

BACKGROUND: Little is known about the determinants of airway hyperresponsiveness (AHR) among children with asthma in Hispanic America. METHODS: We examined the relations among selected familial and environmental factors, markers of allergy, spirometric measures of lung function, and AHR in a cross-sectional study of 403 Costa Rican children with asthma between the ages of 6 and 14 years. Study participants completed a protocol that included questionnaires, spirometry, measurements of serum total and allergen-specific IgE, peripheral blood eosinophil count, and body mass index, and the assessment of airway responsiveness to methacholine (ie, a methacholine challenge test [MCT]). AHR to MCT was defined as the provocative dose of methacholine causing a 20% fall in FEV(1). Linear regression was used for the univariate and multivariate analyses. RESULTS: Of the 403 asthmatic children who underwent an MCT, 350 (86.8%) had AHR to methacholine. In a multivariate analysis, paternal asthma (p = 0.004), parental report of mold/mildew in the child's home (p = 0.04), FEV(1)/FVC ratio (p < 0.0001), and a positive IgE response to Der p 1 (p = 0.008) were significantly associated with AHR among Costa Rican children with asthma. CONCLUSION: Our results suggest that paternal asthma and environmental exposure to mold/mildew are strong determinants of AHR in Costa Rican children with asthma. FEV(1)/FVC ratio may be a useful measure of AHR (a marker of asthma severity) among Costa Ricans and other Hispanic Americans for whom reference values for FEV(1) are not currently available.     

Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy

STUDY OBJECTIVES: To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]). DESIGN AND SETTING: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center. PARTICIPANTS: Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months. MEASUREMENTS AND RESULTS: The groups were similar demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/- 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment. CONCLUSIONS: Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.     

Patient-reported and physician-reported depressive conditions in relation to asthma severity and control

BACKGROUND: Depressive conditions in asthma patients have been described mostly from patient reports and less often from physician reports. While patient reports can encompass multiple symptoms, physician assessments can attribute symptoms to a mental health etiology. Our objectives were to identify associations between patient- and physician-reported depressive conditions and asthma severity and control. METHODS: Patient-reported depressive symptoms were obtained using the Geriatric Depression Scale (GDS) [possible score 0 to 30; higher score indicates more depressive symptoms]. Patients were categorized as having a physician-reported depressive disorder if they had the following: a diagnosis of depression, depressive symptoms described in medical charts, or were prescribed antidepressants at doses used to treat depression. Patients also completed the Severity of Asthma Scale (SOA) [possible score 0 to 28; higher score indicates more severe] and the Asthma Control Questionnaire (ACQ) [possible score 0 to 6; higher score indicates worse control]. RESULTS: Two hundred fifty-seven patients were included in this analysis (mean age, 42 years; 75% women). Mean SOA and ACQ (+/- SD) scores were 5.9 +/- 4.2 and 1.4 +/- 1.2, respectively; and mean GDS score was 6.3 +/- 6.4. After adjusting for age, sex, race, Latino ethnicity, education, medication adherence, body mass index, and smoking status, patient-reported depressive symptoms were associated with asthma severity (p = 0.007) and with asthma control (p = 0.0007). In contrast, physician-reported depressive disorders were associated with asthma severity (p = 0.04) but not with asthma control (p = 0.22) after adjusting for covariates. CONCLUSIONS: Physician- and patient-reported depressive conditions were associated with asthma severity. In contrast, patient-reported depressive symptoms were more closely associated with asthma control than were physician-reported depressive disorders. Identifying associations between depressive conditions and asthma severity and control is necessary to concurrently treat these conditions in this population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00195117.     

FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

Central airway mechanics and flow limitation in acquired tracheobronchomalacia

BACKGROUND: Acquired tracheobronchomalacia (TBM) can cause central airway collapse in patients with COPD and may worsen airflow obstruction and symptoms. It is usually not known whether central airway malacia contributes to airflow obstruction. This study was undertaken to quantify central airway collapsibility and relate it to expiratory flow limitation in patients with TBM. METHODS: Eighty patients evaluated for acquired TBM and 4 healthy control subjects were studied with measurements of central airway narrowing derived from bronchoscopic videotapes and simultaneous pressure measurements in the trachea and esophagus. Tracheal narrowing was assessed by a shape index and plotted against the transtracheal pressure to measure collapsibility. Subsequently, airflow and transpulmonary pressure (PL) were measured to identify expiratory flow limitation during quiet breathing and to determine the critical PL required for maximum expiratory flow. RESULTS: Tracheal collapsibility varied widely among patients. Some had profound tracheal narrowing during quiet breathing, and others showed substantial collapse only during forced exhalation. Of the patients, 15% were not flow limited during quiet breathing, 53% were flow limited throughout exhalation, and 30% were flow limited only during the latter part of the exhalation. Patients with flow limitation at rest showed greater tracheal narrowing than those without (p = 0.009), but the severity of expiratory flow limitation was not closely related to tracheal collapsibility. Twenty-three patients were flow limited during quiet exhalation at PLs that did not cause central airway collapse. CONCLUSIONS: In TBM, central airway collapse is not closely related to airflow obstruction, and expiratory flow limitation at rest often occurs in peripheral airways without central airway collapse.     

Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Area of residence, birthplace, and asthma in Puerto Rican children

RATIONALE: Puerto Ricans have the highest prevalence of asthma among all ethnic groups in the United States. There have been no studies that directly compare the burden of asthma between Puerto Ricans living in Puerto Rico and those living in the mainland United States. OBJECTIVE: To examine the relation between birthplace, area of residence, and asthma in Puerto Rican children. METHODS: Multistage population-based probability sample of children in the San Juan and Caguas metropolitan areas in Puerto Rico and in the Bronx, NY. Information was collected in a household survey of 2,491 children and their primary caretakers. RESULTS: The overall prevalence of asthma among Puerto Rican children in this study was very high (38.6%). Although children from Puerto Rico had higher socioeconomic status and lower rates of premature birth and prenatal smoke exposure, the prevalence of lifetime asthma was higher in Puerto Rican children living in Puerto Rico than in Puerto Rican children living in the South Bronx (41.3% vs 35.3%, p = 0.01). In multivariable analysis, residence in Puerto Rico was associated with increased odds of lifetime asthma (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.03 to 1.57) and lifetime hospitalization for asthma (OR, 1.47; 95% CI, 1.04-2.07). CONCLUSIONS: Puerto Rican children in Puerto Rico had a higher risk of asthma than Puerto Rican children in the South Bronx, highlighting the need for further examination of the roles of migration, acculturation, and environmental and psychosocial factors on the development of asthma in this high-risk population.     

Silent upper airway resistance syndrome: prevalence in a mixed military population

STUDY OBJECTIVES: The upper airway resistance syndrome (UARS) is a recently described form of sleep-disordered breathing in which transient increases in upper airway resistance result in repetitive EEG arousals. UARS is not associated with apnea or diminished airflow, although snoring and excessive daytime somnolence (EDS) are common. This report describes a subset of patients with UARS diagnosed by polysomnography who do not manifest snoring, which we define as silent upper airway resistance syndrome (SUARS). DESIGN: A retrospective review of all polysomnographies performed at our sleep disorders center during 2000. SETTING: Sleep disorders center of a large, academic, military hospital. PATIENTS: Our center serves military personnel, military retirees, and their dependent families. INTERVENTIONS: Esophageal manometry during polysomnography was routinely performed on patients with hypersomnolence (Epworth sleepiness scale > 10) who demonstrated a total arousal index >or= 10/h and a respiratory disturbance index of < 5/h on prior polysomnography. UARS was definitely diagnosed in patients who demonstrated repetitive increased upper airway resistance (IUAR) associated with brief EEG arousals followed by normalization of esophageal pressure (Pes). IUAR was defined by a pattern of crescendo negative inspiratory Pes of 相似文献   

Continuous positive airway pressure therapy improves cardiovascular autonomic function for persons with sleep-disordered breathing

BACKGROUND: Sleep-disordered breathing (SDB) is an independent risk factor for cardiovascular morbidity. Dysfunction of the cardiovascular autonomic nervous system may be a potential mechanism whereby SDB is linked to cardiovascular disease. Repetitive sympathetic activation during apneic episodes may impair cardiovascular reflex function, and increased sympathetic activity can stimulate renin release. Given that patients with SDB may have reduced cardiovascular autonomic function, the purpose of this study was to determine whether treatment with continuous positive airway pressure (CPAP) for 6 weeks would improve autonomic function. METHODS: Twenty-nine participants with a diagnosis of SDB, who completed 6 weeks of CPAP therapy, were evaluated for cardiovascular autonomic nerve fiber function at baseline and post therapy. Autonomic function tests included the following: R-R interval variation during deep breathing measured by vector analysis (ie, mean circular resultant [MCR]) and expiration/inspiration (E/I) ratio; and the Valsalva maneuver. Participants were also evaluated prior to CPAP therapy for plasma renin activity levels. RESULTS: Participants in this study showed improved cardiovascular autonomic function after 6 weeks of treatment (baseline vs follow-up) as assessed by the mean (+/- SD) MCR (33.2 +/- 22.5 vs 36.9 +/- 24.2, respectively; p < 0.05) and E/I ratio (1.20 +/- 0.12 vs 1.24 +/- 0.14, respectively; p < 0.01). Improved vagal tone was also noted for subjects with elevated renin levels. CONCLUSIONS: Treatment of SDB with CPAP for 6 weeks improved vagal tone and may be beneficial in reducing the risk of developing clinical manifestations of cardiovascular autonomic dysfunction (eg, increased risk of mortality).     

Absence of relationships between tuberculin responses and development of adult asthma with rhinitis and atopy

OBJECTIVE: To investigate the relationship between tuberculin skin responses and the development of adult asthma, rhinitis, and atopy. METHODS: Two hundred fourteen patients with mild-to-moderate asthma accompanied with rhinitis and 220 normal volunteers underwent a medical history, chest radiography, allergen skin-prick testing (SPT), bovine Mycobacterium tuberculosis vaccine (BCG) scar identification, purified protein derivative (PPD) tuberculin skin testing, serum-total and serum-specific IgE measurements, and bronchial provocation (provocative dose of histamine causing a 20% fall in FEV(1) [PD(20)]). RESULTS: Thirty-one normal volunteers (14.1%) and 168 asthma-rhinitis subjects (78.5%) had one or more positive skin test results (p < 0.0001). Neither the presence of a BCG scar nor a history of BCG vaccination had a significant effect on atopy in either group. The rate of PPD positivity had no statistical difference between atopy and nonatopy in both groups. In multivariate logistic regression analysis, the odds ratio for tuberculin reactivity was not related to the level of serum-total IgE nor to the level of serum-specific IgE to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), skin response to DP and DF, and PD(20). Overall, no significant correlations were found between tuberculin skin reactivity and log serum-total IgE or PD(20). CONCLUSION: There is no relationship between history of tuberculosis infection, tuberculin responses, and development of adult bronchial asthma, allergic rhinitis, and atopy. Our study suggests that the protection provided by intradermal BCG vaccination in infants to prevent atopic diseases may be limited in early childhood, when a substantial memory of cellular immune modulation still exists.     

Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been associated with increased morbidity and mortality, principally from cardiovascular disease, but the impact of nasal continuous positive airway pressure (CPAP) therapy is unclear. METHODS: We performed a long-term follow-up study of 168 patients with OSAS who had begun receiving CPAP therapy at least 5 years previously, most of whom had been prospectively followed up, having been the subject of an earlier report on cardiovascular risk factors in OSAS patients. The average follow-up period was 7.5 years. We compared the cardiovascular outcomes of those patients who were intolerant of CPAP (untreated group, 61 patients) with those continuing CPAP therapy (107 patients). RESULTS: CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group (48.3 [interquartile range (IQR), 33.6 to 66.4] vs 36.7 [IQR, 27.4 to 55], respectively; p = 0.02), but age, body mass index, and time since diagnosis were similar. Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up (14.8% vs 1.9%, respectively; p = 0.009 [log rank test]), but no significant differences were found in the development of new cases of hypertension, cardiac disorder, or stroke. Total cardiovascular events (ie, death and new cardiovascular disease combined) were more common in the untreated group than in the CPAP-treated group (31% vs 18%, respectively; p < 0.05). CONCLUSIONS: The data support a protective effect of CPAP therapy against death from cardiovascular disease in patients with OSAS.     

Induced sputum in the very young: a new key to infection and inflammation

BACKGROUND: Chronic inflammation and infection in patients with cystic fibrosis (CF) and other lung diseases begin early, making noninvasive diagnostic techniques vital. As induced sputum (IS) testing is useful in older patients, we investigated its adaptation to young nonexpectorating children. METHODS: Following the inhalation of a 4.5% saline solution, sputum was collected by nasopharyngeal or oropharyngeal suction for culture and testing for inflammatory markers, with paired preceding oropharyngeal cough swabs (OCSs) in a subgroup. Specimens from 48 IS procedures (46 successful) in 20 CF children (median age, 3 years) were compared with 8 specimens from 8 non-CF pulmonary patients (median age, 4.5 years). RESULTS: The procedure was safe, with arterial oxygen saturation remaining at > or = 96%. Cultures from 14 of 46 CF patients (30%) grew Pseudomonas aeruginosa, whereas cultures from 19 of 46 CF patients (41%) had no growth. Cultures from seven of eight non-CF subjects grew bacteria, but none were P aeruginosa. Comparing 29 paired IS and OCS samples, 11 and 5 samples, respectively, cultured P aeruginosa (not significant), whereas 12 and 21 samples, respectively, had no growth (p = 0.02). A correlation was found between the independent inflammatory markers NE and both interleukin (IL)-8 (r = 0.85; p < 0.001) and the percentage of neutrophils (r = 0.35; p < 0.05), confirming the validity of IS samples in evaluating early airway disease. IL-8 levels also increased with age (r = 0.41; p < 0.05). Inflammation was similar in CF and non-CF subjects. CONCLUSIONS: IS testing in the young is feasible, safe, and clinically useful, and could serve as an outcome measure for new therapies.     

Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension

BACKGROUND: We have reported previously that the sympathetic nervous system is activated in patients with pulmonary arterial hypertension (PAH), and that this is only partly explained by a decrease in arterial oxygenation. Possible causes for increased muscle sympathetic nerve activity (MSNA) in patients with PAH include right atrial distension and decreased cardiac output. Both may be improved by atrial septostomy, but this intervention also further decreases arterial oxygenation. In the present study, we wanted to investigate the effect of atrial septostomy on MSNA in patients with PAH. METHODS: We recorded BP, heart rate (HR), arterial O2 saturation (SaO2), and MSNA before and after atrial septostomy in PAH patients (mean [+/- SE] age, 48 +/- 5 years) and in closely matched control subjects. Measurements were also performed after septostomy, while SaO2 was brought to the preprocedure level by supplemental O2 therapy. RESULTS: Compared to the control subjects (n = 10), the PAH patients (n = 11) had a lower mean BP (75 +/- 2 vs 96 +/- 3 mm Hg, respectively; p < 0.001), lower mean SaO2 (92 +/- 1% vs 97 +/- 0%, respectively; p < 0.001), increased mean HR (84 +/- 4 vs 68 +/- 3 beats/min; p < 0.01), and markedly increased mean MSNA (76 +/- 5 vs 29 +/- 2 bursts per minute; p < 0.001). Atrial septostomy decreased mean SaO2 (to 85 +/- 2%; p < 0.001) and mean MSNA (to 69 +/- 4 bursts per minute; p < 0.01), but did not affect HR or BP. Therapy with supplemental O2 did not affect MSNA, BP, or HR. The decrease in MSNA was correlated to the decrease in right atrial pressure (r = 0.62; p < 0.05). CONCLUSIONS: Atrial septostomy in PAH patients decreases sympathetic hyperactivity despite an associated decrease in arterial oxygenation, and this appears to be related to decreased right atrial distension.