Bronchodilator Efficacy of High-Flow Nasal Cannula in COPD: Vibrating Mesh Nebulizer Versus Jet Nebulizer.

BACKGROUND: Jet nebulizers are commonly used for bronchodilator therapy in COPD. High-flow nasal cannula with vibrating mesh nebulizer (HFNC-VMN) is a recently developed system; however, few studies have compared the efficacy of bronchodilator administration via HFNC-VMN to jet nebulizer in stable COPD. This study aimed to compare the effect of salbutamol administered via HFNC-VMN versus jet nebulizer on airway and lung function in subjects with stable COPD. METHODS: This randomized non-inferiority crossover physiologic study enrolled subjects with stable COPD. Salbutamol was nebulized via HFNC-VMN or jet nebulizer in random order with a 4-h washout period between crossover sequences. Spirometry, lung volume, and impulse oscillometry were performed at baseline and after each intervention. The primary outcome was change in FEV1 from baseline. Secondary outcomes included changes in other respiratory-related parameters and nebulization time compared between the 2 devices. RESULTS: Seventeen subjects were enrolled. HFNC-VMN and jet nebulizer both significantly improved FEV1 from baseline (P = .005 and P = .002, respectively). The difference between respiratory resistance at 5 Hz and 20 Hz significantly decreased after HFNC-VMN compared to baseline (P = .02), while no significant change was observed after jet nebulizer (P = .056). Area of reactance and resonant frequency of reactance were both significantly decreased (P = .035 and P = .03, respectively), and respiratory reactance at 5 Hz significantly increased (P = .02) in the HFNC-VMN group compared to baseline indicating improved lung mechanics, with no significant changes with the jet nebulizer. HFNC-VMN had a shorter nebulization time (6 [5-9] min vs 20 [16-22] min, respectively, P < .001). CONCLUSIONS: Bronchodilator therapy via HFNC-VMN was not inferior to jet nebulizer for subjects with stable COPD and can significantly improve airway oscillometry mechanics and decrease nebulization time compared to jet nebulizer.

Cognitive impairment according to Montreal Cognitive Assessment independently predicts the ability of chronic obstructive pulmonary disease patients to maintain proper inhaler technique.

BACKGROUND: Maintaining correct inhaler technique is crucial in the management of chronic obstructive pulmonary disease (COPD). We aimed to investigate the inhaler technique in patients with COPD, to compare it immediately after and at 1 month after training, and to identify the predictors of incorrect inhaler use at 1 month after training. METHODS: This prospective study was conducted at the COPD clinic of Siriraj Hospital (Bangkok, Thailand). Patients demonstrating improper inhaler use were trained face-to-face by pharmacists. Inhaler technique was re-assessed immediately after and at 1 month after training. The Montreal Cognitive Assessment (MoCA) score, pulmonary function tests, 6-min walk distance (6 MWD), modified Medical Research Council scale score, and COPD Assessment Test (CAT) score were evaluated. RESULTS: Sixty-six patients with COPD who demonstrated at least one critical error during the use of any controller inhaler were enrolled. The mean age was 73.0 ± 9.0 years, and 75.8% patients had moderate/severe COPD. Immediately after training, all patients used dry powder inhalers correctly and 88.1% used pressurized metered-dose inhalers correctly. At 1 month, the number of patients demonstrating the correct technique decreased across all devices. Multivariable analysis revealed that MoCA score ≤ 16 was independently associated with a critical error at 1 month after training (adjusted odds ratio: 12.7, 95% confidence interval: 1.8-88.2, p = 0.010). At 1 month, CAT score (11.4 ± 8.9 vs. 8.4 ± 5.5, p = 0.018) and 6 MWD (351 ± 93 m vs. 372 ± 92 m, p = 0.009) had significantly improved in patients demonstrating the correct technique, and CAT score met the minimal clinically important difference. CONCLUSIONS: Face-to-face training by pharmacists improved patient performance. However, the number of patients following proper technique had decreased at 1 month after training. Cognitive impairment (MoCA score ≤ 16) independently predicted the ability of COPD patients to maintain proper inhaler technique. Assessment of cognitive function combined with technical re-assessment and repeated training should improve COPD management.

Characteristics, complications, and mortality of respiratory syncytial virus compared with influenza infections in hospitalized adult patients in Thailand.

INTRODUCTION: RSV is increasingly recognized in adults. An improved understanding of clinical manifestations and complications may facilitate diagnosis and management. METHODS: This was a retrospective study of hospitalized patients aged ≥ 18 years with RSV or influenza infection at Siriraj hospital, Thailand between January 2014 and December 2017. RESULTS: RSV and/or influenza were detected by RT-PCR in 570 (20.1%) of 2836 patients. After excluding patients coinfected with influenza A and B (n = 5), and with influenza and RSV (n = 3), 141 (5.0%) RSV and 421 (14.8%) influenza patients were analyzed. Over the study period, RSV circulated during the rainy season and peaked in September or October. Patients with RSV were older than patients with influenza and presented significantly less myalgia and fever, but more wheezing. Pneumonia was the most common complication, occurring in 110 (78.0%) of RSV cases and in 295 (70.1%) of influenza cases (p = 0.069). Cardiovascular complications were found in 30 (21.3%) RSV and 96 (22.8%) influenza (p = 0.707), and were reasons for admission in 15 (10.6%) RSV and 50 (11.9%) influenza. The in-hospital mortality rates for RSV (17; 12.1%) and influenza (60; 14.3%) were similar (p = 0.512). CONCLUSIONS: In Thailand, RSV is a less common cause of adult hospitalization than influenza, but pulmonary and cardiovascular complications, and mortality are similar. Clinical manifestations cannot reliably distinguish between RSV and influenza infection; laboratory-confirmed diagnosis is needed.

Ultrasound Evaluation of Diaphragm Force Reserve in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Diaphragm function is a key determinant of dyspnea in chronic obstructive pulmonary disease (COPD); however, it is rarely assessed in clinical practice. Lung hyperinflation can also impair diaphragm function. Ultrasound can assess the activity, function, and force reserve of the diaphragm.Objectives: To compare diaphragm activity, function, and force reserve among patients with COPD and healthy control subjects.Methods: Patients with stable COPD (n = 80) and healthy control subjects (n = 20) were enrolled (97% of them were men). Ultrasound was used to measure the thickening fraction of the diaphragm during tidal breathing and maximum volitional effort. Outcome measures were as follows: 1) the difference in diaphragm force reserve, activity, and function between patients with COPD and control subjects; 2) the correlation between lung volumes and diaphragm force reserve, activity, and function; and 3) the relationship between diaphragm force reserve and the rate of moderate to severe exacerbation of COPD.Results: The tidal thickening fraction of the diaphragm during resting breathing (TFdi-tidal) was higher in patients with COPD than in control subjects (P = 0.002); it was approximately twice as high in patients with severe COPD than in control subjects. Patients with COPD had poorer diaphragm function than control subjects as assessed by the maximal thickening fraction of the diaphragm during Muller maneuver (P < 0.01). Diaphragm force reserve ratio assessed by 1-(tidal thickening fraction of the diagphragm during resting breathing/maximal thickening fraction of the diaphragm) was lower in patients with COPD than in control subjects, and it fell with increasing Global Initiative for Chronic Obstructive Lung Disease stages (P < 0.001); it correlated with inspiratory capacity (r = 0.46) and the body mass index, airflow obstruction, dyspnea, exercise capacity (BODE) index, a multidimensional scoring system (r = -0.49). Patients who developed exacerbation during the following 2 years had less force reserve than patients without exacerbation (P = 0.024).Conclusions: Male patients with COPD have increased diaphragm workload, impaired diaphragm function, and reduced force reserve compared with healthy subjects. Ultrasound assessment of the diaphragm in COPD provides important functional information.Clinical trial registered with the Thai Clinical Trials Registry (TCTR20160411001). Registered 31 April 5, 2016.

Comparison of immunogenicity between intradermal and intramuscular injections of repeated annual identical influenza virus strains post-pandemic (2011-2012) in COPD patients.

We compared the antibody responses and persistence of the reduced-dose, 9 µg hemagglutinin (HA)/strain intradermal (ID) injection via the Mantoux technique and the 15 µg HA/strain intramuscular (IM) injection of the repeated annual identical trivalent, inactivated, split-virion vaccine 2011-2012 in chronic obstructive pulmonary disease (COPD) patients. Eighty patients were randomized to ID (n = 41) and IM (n = 39) groups. Four weeks post-vaccination, the antibody responses of the two groups were similar; those for influenza A(H1N1)pdm09 and influenza A(H3N2)-but not influenza B-met the criteria of the Committee for Proprietary Medicinal Products (CPMP). The antibody responses for influenza A(H1N1)pdm09 rapidly declined in both groups, especially with the ID injection, whereas those for influenza A(H3N2) maintained above the CPMP criteria throughout 12 months post-vaccination. The geometric mean titres for influenza A(H1N1)pdm09 persisted above the protective threshold (≥ 40) until 6 months post-vaccination in both the ID and IM groups. The seroprotection rates of the ID and IM groups were above 60% until 3 months and 6 months post-vaccination, respectively. In conclusion, the 9 µg HA/strain ID injection of vaccine 2011-2012 elicited antibody responses similar to the standard dose of 15 µg of the HA/strain IM injection at 4 weeks post-vaccination. However, the antibody responses for influenza A(H1N1)pdm09 rapidly declined, especially in the case of the ID injection, whereas they were comparable for influenza A(H3N2). Additional strategies for increasing vaccine durability should be considered, especially for new pandemic strains affecting elderly COPD patients.

Effectiveness of Incentive Spirometry on Inspiratory Muscle Strength After Coronary Artery Bypass Graft Surgery.

BACKGROUND: Although the use of incentive spirometry with a deep breathing exercise (DBE) is widely used in clinical practice in patients who have undergone coronary artery bypass graft (CABG) surgery, the effect of this combination therapy has not been conclusively elucidated. The aim of this study was to investigate the effect of postoperative combined incentive spirometry and DBE versus DBE alone on inspiratory muscle strength following CABG. METHOD: This randomised clinical trial was conducted in patients scheduled to undergo CABG surgery at Siriraj Hospital, Bangkok Thailand. The study group received incentive spirometry and DBE, and the control group received DBE only. Maximal inspiratory pressure (MIP) before surgery and at day 4 after surgery was assessed by a respiratory pressure meter. Secondary outcomes, including postoperative pulmonary complication and duration of postoperative hospitalisation, were obtained from the medical records. RESULTS: Ninety (90) patients were included, with 47 and 43 patients assigned to the study and control groups, respectively. In both groups, there was a significant reduction in MIP from preoperative baseline to postoperative day 4; however, the MIP in the incentive spirometry group had a significantly smaller reduction in MIP compared with the control group (33.0±23.2% vs 47.2±20.1%, respectively; p=0.006, 95% confidence interval, 3.9-23.3). There was no difference between groups regarding secondary outcomes. CONCLUSIONS: Patients in the study group had significantly better recovery of inspiratory muscle strength on day 4 post-CABG than patients in the control group. There was no significant difference between groups for either postoperative pulmonary complications or length of hospital stay.

Clinical manifestations and outcomes of respiratory syncytial virus infection in adult hospitalized patients.

BACKGROUND: Respiratory syncytial virus (RSV) is an important virus found in adult hospitalized patients. OBJECTIVES: To study the clinical outcomes of hospitalized patients aged ≥ 15 years and diagnosed with RSV infection. STUDY DESIGN: Both retrospective and prospective cohort studies were conducted at a university hospital between May 2014 and December 2015. RESULTS: RSV was detected in 86 of 1562(5.5%) adult hospitalized patients suspected of respiratory viral infection. Sixty-nine patients were included in the study. RSV was detected by RT-PCR (82.6%), IFA (10.1%), and both RT-PCR and IFA (7.3%). Most patients (87.0%) were aged ≥ 50 years. Cardiovascular diseases, pulmonary diseases, immunocompromised hosts, and diabetes were the major comorbidities. The common manifestations were cough (92.8%), dyspnea (91.3%), sputum production (87.0%), tachypnea (75.4%), wheezing (73.9%), and fever (71.0%). Fifty- five patients (79.7%) were diagnosed with pneumonia. Hypoxemia (SpO2 ≤ 92%) was found in 53.6% patients. Twenty-five of 69(36.2%) patients developed respiratory failure and required ventilatory support. Cardiovascular complications were found in 24.6% of patients. Congestive heart failure, acute myocardial infarction (MI), new atrial fibrillation, and supraventricular tachycardia were found in 9(13.0%), 7(10.1%), 4(5.8%), and 3(4.3%) of 69 patients, respectively. Overall mortality was 15.9%. Pneumonia (81.8%) and acute MI (18.2%) were the major causes of death. CONCLUSIONS: Most adult hospitalized patients with RSV infection were of advanced age and had comorbidities. Cardiopulmonary complications were the major causes of death. Management and prevention of RSV infection in these vulnerable groups are necessary.

Correlation of vitamin D binding protein gene polymorphism and protein levels in chronic obstructive pulmonary disease compared with non-chronic obstructive pulmonary disease subjects.

AIM: The risk of vitamin D binding protein (DBP) variations in chronic obstructive pulmonary disease (COPD) compared with non-COPD Thai males were investigated. MATERIALS & METHODS: The rs7041 and rs4588 polymorphisms of the DBP gene and protein level were measured in 136 COPD and 68 non-COPD Thai males. RESULTS: In the COPD group, GC1-1 gave increased forced expiratory volume at 1 s % predicted compared with GC1-2 but with no significant difference. Significantly lower average DBP serum levels were observed in COPD than non-COPD subjects. Positive correlation between serum DBP and forced expiratory volume at 1 s % predicted was observed in non-COPD subjects. DISCUSSION & CONCLUSION: DBP variations might be associated with risk factors in COPD caused by both inflammatory and vitamin D circulation processes.

Burden of respiratory disease in Thailand: Results from the APBORD observational study.

Asia-Pacific Burden of Respiratory Diseases (APBORD) was a cross-sectional, observational study examining the burden of respiratory disease in adults across 6 Asia-Pacific countries.This article reports symptoms, healthcare resource utilization (HCRU), work impairment and cost burden associated with allergic rhinitis (AR), asthma, chronic obstructive pulmonary disease (COPD), and rhinosinusitis in Thailand.Consecutive participants aged ≥18 years with a primary diagnosis of AR, asthma, COPD, or rhinosinusitis were enrolled at 4 hospitals in Thailand during October 2012 and October 2013. Participants completed a survey detailing respiratory symptoms, HCRU, work productivity, and activity impairment. Locally sourced unit costs were used in the calculation of total costs.The study enrolled 1000 patients. The most frequent primary diagnosis was AR (44.2%), followed by rhinosinusitis (24.1%), asthma (23.7%), and COPD (8.0%). Overall, 316 (31.6%) of patients were diagnosed with some combination of the 4 diseases. Blocked nose or congestion (17%) and cough or coughing up phlegm (16%) were the main reasons for the current medical visit. The mean annual cost for patients with a respiratory disease was US$1495 (SD 3133) per patient. Costs associated with work productivity loss were the principal contributor for AR and rhinosinusitis patients while medication costs were the highest contributor for asthma and COPD patients.The study findings highlight the burden associated with 4 prevalent respiratory diseases in Thailand. Thorough investigation of concomitant conditions and improved disease management may help to reduce the burden of these respiratory diseases.

Impact of GLI-2012 Spirometric References and Lower Limit of Normal on Prevalence of COPD in Older Urban Thai Persons.

BACKGROUND: Previous analysis of survey data from a study in older urban Thai persons reported prevalence of chronic obstructive pulmonary disease (COPD) of 7.11% according to formerly recommended criteria that used fixed ratio (70%) of pre-bronchodilator FEV1/FVC as the cut-off value. In 2012, the Global Lung Initiative (GLI)-2012 equations for spirometric reference were established and the diagnostic criteria for COPD were changed. OBJECTIVE: To reanalyze the data collected during the 2002 respiratory health survey to determine prevalence of COPD in older urban Thai persons according to the new GLI-2012 equations. MATERIAL AND METHOD: Demographic and clinical data of 3,094 subjects aged ≥ 60 years from 124 urban communities were re-analyzed. Prevalence of COPD determined by post-bronchodilator FEV1/FVC and GLI-2012 equations using lower limit of normal by the Lambda-Mu-Sigma method (LMS-LLN) was compared to COPD prevalence findings based on criteria used in previous analysis. RESULTS: Prevalence of COPD in the study population using post-bronchodilator FEV1/FVC and LMS-LLN was 6.50% (95% CI: 5.63-7.3 7), compared with 7.82% (95% CI: 6.87-8.77) when fixed ratio (70%) of FEV1/FVC was used as cut-off. Diagnostic agreement of COPD between LMS-LLN and fixed ratio was high (kappa 0.88, p < 0.0001). However 45/242 (18.6%) subjects diagnosed as COPD by fixed ratio criteria were considered as "over-diagnosed" when LMS-LLN was used as the standard cut-off The same comparison applied to subjects aged 80 years revealed an increased rate of over-diagnosis to 7/22 (31.8%) subjects. Higher agreement was observed (kappa 0.95, p < 0.0001) when comparing between cut-offs for diagnosis of "at least GOLD stage II" COPD. CONCLUSION: Prevalence of COPD in older urban Thai persons was lower when LMS-LLN was substituted for fixed ratio (70%) of FEV1/FVC. Agreement in COPD diagnosis between both criteria was high, but a substantial proportion of subjects may be over-diagnosed

The immunogenicity of the intradermal injection of seasonal trivalent influenza vaccine containing influenza A(H1N1)pdm09 in COPD patients soon after a pandemic.

The antibody responses of a reduced-dose intradermal seasonal influenza vaccination have never been studied in COPD patients soon after a pandemic. A total of 149 COPD patients (60 y of age or older) were randomized to receive trivalent influenza vaccine (Sanofi-Pasteur, France) either 9 µg of hemagglutinin (HA) per strain split into 2-site intradermal (ID) injections via the Mantoux technique or one intramuscular (IM) injection of 15 µg of HA per strain. The geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates for influenza A(H3N2) and B administered through the ID injection (n = 75) were similar to those obtained with the IM injection (n = 74) 4 weeks post-vaccination. The antibody responses for influenza A(H1N1)pdm09 administered through the ID injection were lower than those obtained with the IM injection, but all of these responses met the 3 criteria proposed by the Committee for Proprietary Medicinal Products (CPMP) for annual re-licensure. The seroprotection rates 4 weeks post-vaccination for influenza A(H1N1)pdm09 were 64.0% (95%CI 52.7-74.0%) in the ID group vs. 78.4% (95% CI 67.6-86.3%) in the IM group (p = 0.053). Influenza-related acute respiratory illness (ARI), diagnosed as a 4-fold rise in HI titers with a convalescent titer > 1:40, and/or the RT-PCR between the ID group (5.3%) and the IM group (8.1%) were not significantly different. The reduced-dose intradermal influenza vaccine may expand vaccine coverage in cases of vaccine shortage.

Pathological confirmed diagnosis of asbestosis: the first case report in Thailand.

Asbestosis is an occupational lung disease defined as pulmonary fibrosis caused by asbestos. Asbestosis was previously reported in Thailand based on radiologic findings, which demonstrated interstitial lung with calcified pleural plaques, and the patient worked in a fiber cement factory. However there was some doubt about the diagnosis because clinical and radiological findings are nonspecific; there was no data support of asbestos exposure in the patient and no histologic confirmed diagnosis. Histologic diagnosis is most useful when an equivocal of ahistory of asbestos exposure in patients with interstitial lung diseases take place. The authors report a patient presenting with progressive dyspnea for 2 years. She worked in an electric, wire, mesh fan cover factory to check quality of protective wire mesh for 10 years until the factory was closed 6 years ago. This type of factory had never officially reported asbestos use. Her clinical manifestations and radiologic findings are compatible with interstitial lung disease. She subsequently underwent thoracotomy with wedge lung resection. Pathology revealed interstitial fibrosis with honeycombing. Asbestos bodies were found more than 10 per cm2 in the fibrosis. She was diagnosed asbestosis. The patient is suffering from dyspnea, severe hypoxemia and cor pulmonale. The patient is put on waiting lists for heart lung transplantation. The authors thus confirmed that asbestosis exists in Thailand. A policy to protect workers and people who may have risk of asbestos exposure is necessary, since diseases related to asbestos are incurable, but preventable.

Substrate utilization during and after high intensity exercise in healthy lean and obese men.

OBJECTIVE: To compare lipid and carbohydrate use during and after a high-intensity endurance exercise bout between lean and obese subjects. MATERIAL AND METHOD: Lean and obese healthy male subjects with energetic physical activity and stable body weight were recruited to participate in the present study. The respiratory exchange ratio (RER), lipid and carbohydrate oxidation, and lipid and carbohydrate energy expenditure during resting condition, high-intensity exercise and 180 min after exercise were determined by indirect calorimetry RESULTS: Ten lean and ten obese healthy male subjects, aged 26+/-4 years, completed a 300-kcal high-intensity exercise session. Resting energy expenditure and lipid energy expenditure in the obese group were significantly higher than those of the lean group. The RER, lipid oxidation, and carbohydrate oxidation were not significantly different between groups throughout the exercise period. The total energy expenditure and total lipid and carbohydrate energy expenditure were also not significantly different between lean and obese groups. During the 180-minute post exercise period, both lean and obese subjects showed a declination in RER and carbohydrate oxidation and an increase in lipid oxidation. CONCLUSION: Substrate use during and after high-intensity exercise between healthy lean and obese subjects was not significantly different. Both groups used carbohydrates and lipids as the main substrate sources during and after high-intensity exercise, respectively.

Relationship between emphysema quantification and COPD severity.

OBJECTIVE: To determine the association between emphysema extent from high-resolution computed tomography (HRCT) and the physiological derangement in patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHOD: A cross-sectional study was undertaken to quantify the emphysema severity in 23 COPD patients by automated HRCT scoring techniques. Correlation with phenotypic characters in term of exercise capacity [Modified Medical Research Council (mMRC) dyspnea scale, and 6-minute walk distance (6MWD)], pulmonary function testing [spirometry (forced expiratory volume in 1 second, FEV1 and forced vital capacity, FVC), and diffusing capacity (DLCO)], were then assessed. RESULTS: Nineteen patients were male and four were female, the mean age was 73 ± 8 years, with the mean FEV1 % predicted of 67.8 ± 25.4. Percentage of inspiratory emphysematous lung volume (%ELVi) had significant negative correlation with %FEV/FVC (r = -0.50, p = 0.016) and DLCO (r = 0.58, p = 0.011). Percentage of expiratory emphysematous lung volumes (%ELVe) also had the same correlation with %FEV/FVC (r = -0.58, p = 0.004) and DLCO (r = 0.48, p = 0.042). In addition, %ELVe also had significant negative correlation with 6MWD (r = 0.50, p = 0.016), but had significant positive correlation with mMRC scale (r = 0.53, p = 0.01). CONCLUSION: Severity of emphysema assessed by HRCT was well correlated with pulmonary function test results and exercise capacity. It can be used as one aspect ofphenotypic characters in patients with COPD,for designing personalize management plan.

Prevalence of osteoporosis and osteopenia in Thai COPD patients.

OBJECTIVE: To study the prevalence of osteoporosis and osteopenia in Thai COPD patients and the factors associated with osteoporosis. MATERIAL AND METHOD: A cross sectional study was used to evaluate 102 male stable COPD patients. Bone mineral density at lumbar spine (L2-4) and femoral neck were measured by dual energy x-ray absorptiometer scan. Demographic data including age, body mass index (BMI), inhaled corticosteroids use, tobacco smoke, force expiratory volume at 1 second (FEV1), and high sensitivity C-reactive protein (hs-CRP) were analyzed. RESULTS: The overall prevalence of osteoporosis and osteopenia according to the lowest T-score at either L2-4 or femoral neck were 31.4% and 32.4%, respectively. This prevalence of osteoporosis in COPD patients was higher than that in age-matched Thai males from historical data (31.4% vs. 12.6%, respectively). BMI and hs-CRP were significantly associated with osteoporosis. There was no association between osteoporosis and severity of COPD, age, smoking, and corticosteroid use. The predictive value of BMI < 20.5 kg/m2 and hs-CRP > 2.3 mg/L demonstrated risk of osteoporosis in COPD patients (adjusted Odds ratio 7.2 and 4.1, respectively). CONCLUSION: The prevalence of osteoporosis and osteopenia in Thai COPD patients was higher than that in normal age-matched Thai males. Osteoporosis was associated with low BMl and high level of hs-CRP when compared to COPD patients with normal bone mineral density.

The immunogenicity of intradermal influenza vaccination in COPD patients.

We evaluated the immunogenicity of a reduced-dose intradermal trivalent, inactivated, split-virion seasonal influenza vaccine compared to that of a conventional intramuscular vaccination in chronic obstructive pulmonary disease (COPD) patients. One hundred and fifty-six COPD patients randomly received either 0.2 ml (6 microg hemagglutinin (HA) per strain) split into two-site intradermal (ID) injections or a single 0.5 ml (15 microg HA per strain) intramuscular (IM) injection. Geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates at 4 weeks post-vaccination in the ID group were less than those in the IM group. Only the seroconversion factor to influenza B in the ID group was statistically less than in the IM group (18.8 in the ID group, n=81 versus 37.3 in the IM group, n=75, p=0.045). Nevertheless, each strain of the ID vaccination met all the Committee for Proprietary Medicinal Products (CPMP) criteria. Seroprotection rates were above 60% throughout the year in influenza A (H3N2), for at least 6 months in influenza A (H1N1) and at least 4 weeks in influenza B in both ID and IM groups. The reduced-dose intradermal vaccination may be considered for use in COPD patients in a vaccine shortage situation.

Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs.

We addressed the hypothesis that single vagal afferent C-fibres can be stimulated via either the adenosine A1 or A2A receptor subtypes. The effect of adenosine on the nerve terminals of vagal sensory nerve subtypes was evaluated in an ex vivo perfused guinea pig lung preparation using extracellular recording techniques. Adenosine (10 microm) consistently evoked action potential discharge in lung C-fibre terminals arising from the nodose ganglia, but failed to evoke action potential discharge in most jugular ganglion C-fibres. Adenosine also failed to activate stretch-sensitive nodose A-fibres in the lungs. The selective A1 antagonist DPCPX (0.1 microm) or the selective A2A antagonist SCH 58261 (0.1 microm) partially inhibited the nodose C-fibre activation by adenosine, and the combination of both antagonists almost completely inhibited the response. The adenosine-induced action potential discharge in nodose C-fibres was mimicked by either the selective A1 agonist CCPA (1 microm) or the selective A2A agonist CGS 21680 (1 microm). Single cell PCR techniques revealed that adenosine A1 and A2A receptor mRNA was expressed in individual nodose neurons retrogradely labelled from the lungs. The gramicidin-perforated patch clamp technique on neurons retrogradely labelled from the lungs was employed to study the functional consequence of adenosine receptor agonists directly on neuronal membrane properties. Both the selective A1 agonist CCPA (1 microm) and the selective A2A agonist CGS 21680 (1 microm) depolarized the airway-specific, capsaicin-sensitive, nodose neurons to action potential threshold. The data support the hypothesis that adenosine selectively depolarizes vagal nodose C-fibre terminals in the lungs to action potential threshold, by stimulation of both adenosine A1 and A2A receptor subtypes located in the neuronal membrane.

Allergen-induced substance P synthesis in large-diameter sensory neurons innervating the lungs.

BACKGROUND: Tachykinins such as substance P are localized in unmyelinated slow-conducting C fibers that can be activated by noxious stimuli and tissue inflammation. Substance P is seldom expressed in fast-conducting large-diameter (A-fiber) vagal sensory neurons. We have previously found that allergic inflammation causes a phenotypic change in tachykinergic innervation of the trachea such that the production of substance P is induced in large-diameter sensory neurons projecting mechanosensitive A fibers to the trachea. OBJECTIVE: To evaluate whether allergic inflammation also induces substance P synthesis in large-diameter sensory stretch-receptor neurons innervating guinea pig lungs, and to investigate potential mechanisms by which this may occur. METHODS: Sensitized guinea pigs were exposed to allergen (ovalbumin) aerosol. One day later, immunohistochemical analysis was performed on vagal sensory neurons that had been retrogradely labeled from the lungs. RESULTS: Ovalbumin inhalation caused a significant increase in substance P expression in large-diameter neurofilament-positive nodose ganglion neurons that innervate the lungs (P < .05). This effect was decreased by ipsilateral vagotomy. Exposing isolated nodose ganglia to the sensitizing antigen, ovalbumin, also significantly increased substance P expression compared with control. CONCLUSION: Allergic inflammation induces substance P synthesis in large-diameter (A-fiber) nodose ganglion neurons innervating guinea pig lungs. This could contribute to the hyperreflexia seen in allergic airway disease. The full expression of this phenotypic switch in vagus nodose ganglion neurons requires intact vagus nerve, but if allergen reached the systemic circulation in sufficient quantities, it could also affect substance P synthesis by local activation of vagal ganglionic mast cells.

Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs.

5-Hydroxytryptamine (5-HT, serotonin) evokes pulmonary reflexes partially by activating vagal bronchopulmonary C-fibers. In the guinea pig, vagal bronchopulmonary C-fibers arise from cell bodies situated in the nodose and the jugular ganglia. The nodose and the jugular C-fibers differ both pharmacologically and neurochemically, and may subserve different functions. In this study, we compared the effect of 5-HT on the nodose and jugular C-fibers with receptive fields within the guinea pig lungs. The nerve terminals of the vagal bronchopulmonary C-fibers were studied in an ex vivo isolated perfused lung nerve preparation using the extracellular recordings. All nodose C-fibers responded to transient administration of 5-HT (10 microM) and to the selective 5-HT3 receptor agonist, 2-methyl-5-HT (10 microM), with the action potential discharge. The selective 5-HT3 receptor antagonist ondansetron (10 microM) inhibited (by approximately 90%) the activation of the nodose C-fibers evoked by 5-HT (10 microM). In contrast to the nodose C-fibers, the jugular C-fibers were unresponsive or poorly responsive to 5-HT (n=9) and unresponsive to 2-methyl-5-HT (n=11). A direct action of 5-HT on the C-fiber neurons was supported using the whole cell patch clamp recordings from the isolated vagal sensory neurons retrogradely labeled from the lungs. Consistently with the studies on the nerve terminals, 5-HT (10 microM) induced inward current in nodose lung-specific capsaicin-sensitive neurons. Conversely, 5-HT was inefficient to stimulate the lung-specific jugular neurons. We conclude that in the guinea pig lungs, 5-HT selectively stimulates vagal nodose, but not jugular C-fibers via the 5-HT3 receptors in the neuronal membrane.