Respiratory Medicine

Involvement of type II pneumocytes in the pathogenesis of chronic obstructive pulmonary disease

Chun-zhen Zhao, Xiao-cong Fang, Diane Wang, Fa-di Tang, Xiang-dong Wang — 2010-07-21

Summary: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality, but the cellular and molecular mechanisms are still not fully understood. Type II pneumocytes are identified as the synthesizing cells of the alveolar surfactant, which has important properties in maintaining alveolar and airway stability. Lung surfactant can reduce the surface tension and prevent alveolar collapse and the airway walls collapse. Pulmonary surfactant components play important roles in normal lung function and inflammation in the lung. Surfactant has furthermore been shown to modulate the process of innate host defense, including suppression of cytokine secretion and transcription factor activation, in the inflammatory network of COPD. Abnormalities of lung surfactant might be one of the mechanisms leading to increased airway resistance in COPD. The increased expression of Granzyme A and B was found in lung tissues of patients with COPD and type II pneumocytes was proposed to be involved in the pathogenesis of COPD. These novel findings provide new sights into the role of the type II pneumocytes in the pathogenesis of COPD.

Short-course fluoroquinolone therapy in exacerbations of chronic bronchitis and COPD

Antonio Anzueto, Marc Miravitlles — 2010-06-28

Summary: Acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) are associated with significant healthcare costs and contribute to the progress of the disease. Although a number of factors may trigger these episodes, between 40% and 60% are bacterial in nature. Antimicrobial therapy can be effective in treating exacerbations, leading to improved peak expiratory flow rates, fewer hospitalizations, lower relapse rates, and greater clinical success. Evidence suggests that short-course antimicrobial therapy can be as effective as standard duration therapy (>7 days) in treating exacerbations. Randomized trials have shown that clinical and bacteriological success rates are comparable with both 5-day and standard antibiotic courses. Furthermore, 5-day fluoroquinolone therapy is associated with faster recovery, fewer relapses, prolonged duration between episodes, and less hospitalization when compared with standard therapy. Both moxifloxacin and gemifloxacin have received FDA-approval for 5-day therapy in AECB.

Mediators of inflammation in nasal lavage from aspirin intolerant patients after aspirin challenge

2010-05-10

Summary: The pathogenetic mechanisms underlying development of persistent inflammation in aspirin (ASA) intolerance are not fully understood. The aim of this study was to determine levels of MCP-3, RANTES, eotaxin, Il-5 and Il-3 in aspirin intolerant asthmatics (AIA) after nasal lysine–aspirin (Lys–ASA) challenge. Twenty AIA and 10 aspirin tolerant controls (ATC) were challenged with saline or 14.4mg of Lys–ASA. Lys–ASA challenge induced clinical symptoms and influx of eosinophils and basophils only in AIA group. Statistically significant higher levels of MCP-3 and RANTES were found in lavages from AIA as compared with ATC (p<0.05 in all time points). Before challenge the average level of MCP-3 was 86.95pg/ml in AIA and 47.61pg/ml in ATC, RANTES levels were 34.20pg/ml in AIA and 17.21pg/ml in ATC and did not change after the challenge in both group. The mean eotaxin’s level was 11.01pg/ml in AIA and 8.03pg/ml in ATC before and increased to 20.06, 26.22pg/ml (4 and 24h in AIA) as compared to 10.51, 14.76pg/ml (4 and 24h in ATC) after the challenge (p<0.05). Interleukin-3 and Il-5 were not detectable. The highest inhibition of eosinophils’ chemotaxis was induced by anti-eotaxin (47% of inhibition), followed by anti-RANTES (29%), anti-MCP-3 (19%) and anti-Il-5 (9%). In summary, we found that persistent inflammation in AIA patients is characterized by overproduction of MCP-3 and RANTES. Lack of increase in MCP-3 and RANTES levels after Lys–ASA challenge suggest that those mediators are involved in chronic rather than acute phase of ASA induced inflammation.

Italian real-life experience of omalizumab

2010-05-19

Summary: Omalizumab is a humanized murine monoclonal antibody directed toward a portion of the IgE indicated in Europe for the treatment of severe persistent allergic asthma, inadequately controlled despite high-dose of ICS (mean BDP equivalent dose of inhaled corticosteroid 2224.68μg/die) in association with long-acting β2 agonists.Our aim was to describe the experience, efficacy and safety in a cohort of Italian patients treated with omalizumab in a real-life clinical setting. One hundred and forty two patients from 13 Italian Centers were observed and analysed. The dosage of omalizumab was established according to the labelling indication, with a median dose of IgE of 297.38IU/ml or kU/l. During the previous year, all patients experienced frequent exacerbations (mean=4.87), emergency visits (mean=4.45) and hospitalisation (mean=1.53). Following treatment with omalizumab, the annual rate of exacerbations, emergency visits and hospitalisation decreased by 79%, 88% and 95%, respectively. The proportion of patients without exacerbation, not needing emergency visits and hospitalization increased by 610%, 154% and 28%, respectively. The response to omalizumab measured with the GETE (global evaluation of treatment effectiveness) scale rated as good to excellent in 77% of patients. Overall, 9.6% (n=9) of the patients experienced one single adverse effect. Only one patient reported a serious adverse event (local reaction at the site of injection) leading to interruption of treatment. The observed reduction of asthma-related events in particularly poorly controlled patients in this Italian real-life setting is consistent with the results of other observational studies.

Acute additive effect of montelukast and beclomethasone on AMP induced bronchoconstriction

2010-05-17

Summary: Bronchial hyperresponsiveness to 5-adenosine mono-phosphate (AMP) is a marker of airway inflammation. Inhaled corticosteroids and antileukotrienes are used as anti-inflammatory drugs for the treatment of asthma. To find out if these two drugs exert their protection in an additive fashion, we compared the effects of acute treatment with inhaled beclomethasone (BDP) and montelukast (ML), alone or in combination, on methacholine and AMP induced bronchoconstriction.15 asthmatic patients undertook methacholine and AMP challenges at baseline and after receiving ML or BDP, alone or in combination, in a randomized, double-blind, double-dummy placebo-controlled, crossover design.BDP pretreatment significantly increased the AMP PC20 value (68.34±15.9mg/mL) as compared to placebo (22.87±5.7mg/mL). Combined treatment, BDP plus ML, afforded a further significant increase of AMP PC20 (154.57±55.0mg/mL) as compared to each single treatment. The significant protection exerted by combined treatment as compared to each single active treatment was also demonstrated by the change of AMP PC20 doubling dose as compared to placebo and each single active treatment.Our findings suggest that these two agents exert their acute additive protection against AMP induced bronchoconstriction acting on distinct inflammatory pathways and their combined use might provide greater protection against inflammatory response elicited by AMP than either drug alone.

Montelukast added to fluticasone propionate does not alter inflammation or outcomes

2010-08-16

Summary: Background: Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation.Objectives: To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting β2-agonists.Methods: Patients uncontrolled on short-acting β2-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation.Results: Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p≤0.008). Both treatments significantly reduced submucosal mast cell, CD3+, CD4+, CD8+ and CD25+ cell counts. Submucosal mast cell reduction was greater in the fluticasone propionate plus montelukast group. There were no differences between treatments in BAL markers of inflammation or thickness of sub-epithelial collagen.Conclusions: Low-dose fluticasone propionate significantly improves clinical disease control and reduces airway inflammation in asthma patients uncontrolled with short-acting β2-agonists without further improvement when montelukast is added to low-dose fluticasone propionate.

Increases in airway eosinophilia and a th1 cytokine during the chronic asymptomatic phase of asthma

2010-08-16

Summary: Background: Studies using allergen challenge models have suggested Th2 cytokines promote airway inflammation in asthma. We assessed mediators of airway inflammation during the chronic asymptomatic phase of asthma.Methods: Nine non-atopic asthma (NAA) patients, 19 atopic asthma (AA) patients, 20 atopic controls (AC), and 38 normal controls (NC) underwent sputum induction while asymptomatic. Sputum total cell counts and differentials were determined; levels of cytokines IL-4, IL-5, IL-13, GM-CSF, and IFN-γ, and chemokines eotaxin (CCL11) and RANTES (CCL5) were measured by ELISA; and levels of eosinophil-derived neurotoxin (EDN) were measured by radioimmunoassay.Results: NAA patients showed higher % eosinophils and total eosinophils compared to AA. NAA and AA patients showed higher IFN-γ and EDN levels compared to AC and NC, with no differences in IL-4, IL-5, or IL-13 levels among the four groups. GM-CSF levels were higher in AA patients compared to AC or NC. In NAA, AA, and AC patients, % eosinophils and EDN levels correlated positively with IFN-γ, GM-CSF, eotaxin, and RANTES, but not with IL-5 levels.Conclusions: Baseline airway inflammation of intrinsic and extrinsic asthma is characterized by eosinophilic inflammation and the Th1 cytokine, IFN-γ. GM-CSF, instead of IL-5, and chemokines may coordinate airway eosinophilia during the chronic asymptomatic phase of asthma.

Resting respiratory variables and exercise capacity in adult patients with cystic fibrosis

2010-07-02

Summary: Introduction: Cystic fibrosis (CF) is the most common life-limiting, recessively inherited disease in the white population, associated with significantly high morbidity and mortality rates; CF pulmonary disease, assessed by pulmonary function tests, arterial blood gases and the Schwachman score, remains the most prevalent in terms of morbidity in the adult CF population.Objectives: The aim of the present study was to evaluate the relationship between resting respiratory variables and exercise capacity in adult patients with CF.Results: Study investigations undertaken in 18 CF patients and 11 healthy volunteers showed that among the resting lung function parameters, inspiratory capacity (IC) at rest was the only significant predictor of VO2 peak (r=0.67, p<0.007) and VO2/t-slope (r=0.86, p<0.0001). The percentage of predicted FEV1 in adult CF patients was 77±33% pred. vs 104±16% pred. in healthy subjects (p<0.006); the corresponding percentage of IC at rest was 82±36% pred. in patients vs 116±20% pred. in healthy (p<0.003). CF patients presented with a significantly prolonged rapid breathing after exercise (32br per minute at recovery for CF vs 22 for healthy; p<0.001), as well as a shortened inspiratory time.Conclusion: Adult patients with CF show a limited exercise capacity with lower peak oxygen consumption and prolonged oxygen kinetics. Interestingly, decreased IC qualified as the only significant predictor of exercise capacity in our study.

Budesonide added to formoterol contributes to improved exercise tolerance in patients with COPD

2010-08-09

Summary: Background: Breathlessness and exercise intolerance frequently impact the daily life of patients with COPD.Methods: This double-blind, multicentre, three-period crossover study randomised 111 patients with COPD (mean age 64 years, mean FEV1 38% of predicted normal) to budesonide/formoterol 320/9 μg, formoterol 9 μg or placebo, twice daily for 1 week, following a 1-week run-in period with 1-week wash-out between treatments. Terbutaline (0.5 mg/dose) was used as needed. The primary efficacy variable was exercise endurance time (EET) at 75% peak work capacity with cycle ergometry assessed 1 h post-morning dose.Results: Budesonide/formoterol prolonged EET 1 h post-morning dose versus formoterol by 69 s (P < 0.005) and placebo by 105 s (P < 0.0001) and improved inspiratory capacity (IC) at isotime during exercise versus formoterol by 8% (P = 0.011) and placebo by 16% (P < 0.0001). Borg score at isotime was reduced by 0.48 (P = 0.12) and 0.78 (P = 0.014) compared with formoterol and placebo, respectively. At the repeated cycle test 6 h after morning dose, the effect on EET still favoured budesonide/formoterol over formoterol and placebo, while the isotime IC and Borg score were similar but better than placebo for the active study drugs. Budesonide/formoterol and formoterol improved health status (St George’s Respiratory Questionnaire total score: mean difference versus placebo −2.4 and −2.2, respectively). All treatments were well tolerated.Conclusions: Budesonide/formoterol resulted in a significant improvement in endurance time 1 h after the last morning dose in a 1-week treatment period versus formoterol and placebo. This study demonstrates, for the first time, the benefit of inhaled corticosteroids in addition to long-acting β2-agonists on exercise tolerance in COPD patients.www.clinicaltrials.gov registration number: NCT00489853.

A one-year trial of tiotropium Respimat® plus usual therapy in COPD patients

2010-07-12

Summary: In this randomised double-blind study, patients ≥40 years old with COPD, a smoking history of ≥10 pack-years, a pre-bronchodilator FEV1 of ≤60% predicted and an FEV1/FVC of ≤70% received tiotropium 5 μg or placebo via Respimat® inhaler once daily for 48 weeks. Other medications were permitted except inhaled anticholinergics. Co-primary endpoints were trough FEV1 and the time to first exacerbation. Adverse events were followed and vital status regularly assessed.In all, 3991 patients (mean age, 65 years [SD, 9 years]) were evaluable. Mean baseline FEV1 was 1.11 L (0.40 L) or 40% (12%) of predicted normal. Adjusted mean differences in trough FEV1 and trough FVC at Week 48 (tiotropium minus placebo) were 102 and 168 ml respectively (p < 0.0001, both). Tiotropium delayed time to first exacerbation relative to placebo (hazard ratio [HR], 0.69 [95% CI, 0.63–0.77]) and time to first hospital-treated exacerbation (HR, 0.73 [0.59–0.90]). SGRQ score at Week 48 was 2.9 units lower with tiotropium (p < 0.0001). Adverse and serious adverse events were balanced across treatment groups and similar in profile to previous tiotropium trials. The rate ratio for a major adverse cardiovascular event during the treatment period + 30 days was 1.12 (0.67–1.86). By the end of planned treatment (Day 337) 52 patients on tiotropium (incidence rate per 100 years, 2.94) and 38 on placebo (2.13) had died (HR = 1.38 [0.91–2.10]; p = 0.13).Lung function, exacerbations and quality of life were improved by tiotropium 5 μg Respimat® but a numerical imbalance was seen in all-cause mortality.The protocol is registered on the European Clinical Trials Database as trial number 2006-001009-27 and in the ClinicalTrials.gov database as NCT00387088.

Generic, symptom based, exercise rehabilitation; integrating patients with COPD and heart failure

R.A. Evans, S.J. Singh, R. Collier, I. Loke, M.C. Steiner, M.D.L. Morgan — 2010-07-23

Summary: Background: Patients with Chronic Heart Failure (CHF) develop similar symptoms of exertional breathlessness and fatigue as patients with COPD. Although pulmonary (exercise based) rehabilitation (PR) is an integral part of the management of COPD, the potential for exercise rehabilitation (ER) to assist patients with CHF may not be as readily appreciated. We investigated whether combined ER for patients with CHF and COPD was feasible and effective using the model of PR.Methods: 57 patients with CHF were randomized 2:1 to 7 weeks ER (CHF-ER) or 7 weeks of usual care (CHF-UC). As a comparator 55 patients with COPD were simultaneously recruited to the same ER program (COPD-ER). The primary outcome measure was the Incremental Shuttle Walk Test (ISWT) and the secondary outcome measures were the Endurance Shuttle Walk Test (ESWT), isometric quadriceps strength and health status.Results: 27 CHF and 44 COPD patients completed ER and 17 patients with CHF completed UC. The CHF-ER group made significant improvements, compared to CHF-UC, in the mean (95%CI) ISWT distance; 62(35–89)m vs −6(−11 to 33)m p < 0.001. The CHF-ER group also made statistically significant improvements in health status. The improvements in exercise performance and health status were similar between patients with CHF and COPD, treated with ER.Conclusion: Patients with CHF who undergo ER improve similarly in their exercise performance and health status to COPD. Combined training programs for COPD and CHF are effective and feasible, such that service provision could be targeted around common disability rather than the primary organ disease.

Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients

2010-06-14

Summary: NVA237 is a once-daily inhaled long-acting muscarinic antagonist in development for the treatment of COPD.This randomized, double-blind, placebo-controlled, four-period, incomplete block crossover study, with open-label active comparator (tiotropium), assessed the efficacy and safety of NVA237. Patients (≥40 years; smoking history ≥10 pack-years) with stable moderate-to-severe COPD (post-bronchodilator FEV1 ≥ 30% and <80% predicted, FEV1/FVC < 0.7) received NVA237 12.5, 25, 50 or 100 μg, placebo, or tiotropium 18 μg once-daily for 7 days. The primary endpoint was mean trough (23–24 h post-dose) FEV1 on Day 7. Secondary endpoints included mean trough FEV1 on Day 1, and FEV1 and FVC at individual time points post-dose on Days 1 and 7. 83 patients (mean age 64.4 years; male 83.1%; mean COPD duration 6.7 years; mean post-bronchodilator FEV1 1.5 L/52.7% predicted) were randomized; 78 completed. Mean trough FEV1 on Day 7 and Day 1 was significantly higher with all active treatments versus placebo (p < 0.05). NVA237 50 μg, 100 μg and tiotropium showed clinically relevant improvements versus placebo on Day 7 (differences of 131, 142 and 127 mL, respectively; p < 0.0001) and 1 (differences of 121, 135 and 112 mL, respectively; p < 0.0001). On Day 1, but not Day 7, FEV1 was significantly higher (p < 0.05) with NVA237 50 and 100 μg versus tiotropium from 5 min up to 2 and 4 h post-dose, respectively. All doses of NVA237 and tiotropium were well tolerated.NVA237 once-daily was effective and well tolerated versus placebo, and demonstrated rapid and sustained 24-h bronchodilation. (ClinicalTrials.gov Identifier: NCT00501852).

Energy expenditure and impact of bronchodilators in COPD patients

2010-05-14

Summary: 28 Consecutive COPD patients performed four 6-minute walking tests (6-MWTs) in 2 different days before and 2, 4 and 6h after the inhalation of formoterol 12μg or tiotropium 18μg, respectively. Physical activity during each 6-MWT was assessed by the SenseWear® Armband. At each time also spirometry was performed. Both formoterol and tiotropium induced a significantly sustained bronchodilation and influenced hyperinflation. Formoterol significantly increased distance walked in 6min at 2h and at 4h, whereas tiotropium significantly increased it at all time points. There was a trend to an increase in calories and metabolic equivalents of task (METs) after formoterol and a decrease after tiotropium, but changes were not statistically significant. Total energy expenditure for each 6-MWT was not changed by formoterol, but decreased in significant manner 6h after the inhalation of tiotropium. Active energy expenditure at physical activity level of more than 3 METs decreased significantly after tiotropium at each 6-MWT, but not after formoterol. We did not find any significant correlation between the changes in lung function and those of parameters recorded with SenseWear® Armband. Our study seems to indicate that tiotropium, but not formoterol, is able to reduce energy expenditure in COPD patients, although both drugs elicit significant bronchodilation and are able to increase the distance walked in 6min.

Effect of tiotropium in men and women with COPD: Results of the 4-year UPLIFT® trial

Donald Tashkin, Bartolome Celli, Steven Kesten, Ted Lystig, Marc Decramer — 2010-04-26

Summary: Background: Gender differences may occur in many chronic diseases. We have examined the influence of gender in chronic obstructive pulmonary disease (COPD) on long-term responses to tiotropium.Methods: Subgroup analysis of data from the Understanding the Potential Long-term Impact of Tiotropium (UPLIFT®) trial (4-year, randomized, double-blind, placebo-controlled trial of tiotropium in patients with COPD).Results: Of 5992 patients, 75% were men and 25% women. Mean age was 65 and 63 years, respectively. Baseline post-bronchodilator forced expiratory volume in 1s (FEV1)=47% predicted(men) and 49% predicted(women). St George’s Respiratory Questionnaire (SGRQ) total score was 44.9 and 48.7units, respectively. At 48 months, improvement in trough FEV1 over control was 92mL(men) and 77mL(women) (p<0.001 for both), with no differences in the rate of decline (trial primary endpoint). Hazard ratio (HR) (95% confidence interval [CI]) for first exacerbation (tiotropium/placebo) was 0.87(0.81, 0.93)(men) and 0.83(0.74, 0.94)(women). Number of exacerbations (per patient-year) was reduced with tiotropium in men (from 0.82 to 0.71) and women (from 0.92 to 0.77) (p<0.005 for both). HR (95% CI) for a hospitalized exacerbation was 0.89(0.79, 0.99) and 0.77(0.62, 0.94), respectively. HR (95% CI) for mortality during treatment was 0.85(0.72, 0.99)(men) and 0.85(0.62, 1.18)(women). Improvements in SGRQ total score (tiotropium–control) at 1, 2, 3 and 4 years were: −2.8, −2.3, −3.6, −2.4(men) and −2.7, −2.6, −2.6, −2.1(women) (p<0.05 for all).Conclusion: Long-term treatment of COPD with tiotropium improves lung function, exacerbations and health status in men and women, with similar magnitudes of benefit.Boehringer Ingelheim trial 205.235; ClinicalTrials.gov: NCT00144339.

A proposal of a new model for long-term weaning: Respiratory intensive care unit and weaning center

2010-06-14

Summary: Background: Respiratory intermediate care units (RICU) are hospital locations to treat acute and acute on chronic respiratory failure. Dedicated weaning centers (WC) are facilities for long-term weaning.Aim: We propose and describe the initial results of a long-term weaning model consisting of sequential activity of a RICU and a WC.Methods: We retrospectively analysed characteristics and outcome of tracheostomised difficult-to wean patients admitted to a RICU and, when necessary, to a dedicated WC along a 18-month period.Results: Since February 2008 to November 2009, 49 tracheostomised difficult-to wean patients were transferred from ICUs to a University-Hospital RICU after a mean ICU length of stay (LOS) of 32.6 ± 26.6 days. The weaning success rate in RICU was 67.3% with a mean LOS of 16.6 ± 10.9 days. Five patients (10.2%) died either in the RICU or after being transferred to ICU, 10 (20.4%) failed weaning and were transferred to a dedicated WC where 6 of them (60%) were weaned. One of these patients was discharged from WC needing invasive mechanical ventilation for less than 12h, 2 died in the WC, 1 was transferred to a ICU. The overall weaning success rate of the model was 79.6%, with 16.3% and 4.8% in-hospital and 3-month mortality respectively. The model resulted in an overall 39 845 ± 22 578 € mean cost saving per patient compared to ICU.Conclusion: The sequential activity of a RICU and a WC resulted in additive weaning success rate of difficult-to wean patients. The cost-benefit ratio of the program warrants prospective investigations.

Effects of ambient air pollution on lung function growth in Chinese schoolchildren

2010-05-17

Summary: Objective: To evaluate the adverse effect of exposure to air pollution on lung function growth in school-aged children.Methods: A cohort of 1983 children from three districts in Guangzhou, China was followed-up for 6 months. The children performed pulmonary function tests twice, and their parents reported the child’s respiratory symptoms by self-administered questionnaires in both surveys.Results: The annual mean concentrations of air pollutants for the past 5 years for particulate matter less than 10 microns in diameter (PM10), nitrogen (NO2), and sulfur dioxide (SO2) were respectively: 96.1 μg/m3, 76.0 μg/m3, and 65.7 μg/m3 in the highly-polluted district (HPD), 80.3 μg/m3, 67.6 μg/m3, and 54.5 μg/m3 in the moderately-polluted district (MPD), and 80.0 μg/m3, 48.1 μg/m3, and 52.2 μg/m3 in the least-polluted district (LPD).After adjustment for potential confounders, significant deficits were found in the annual growth rates of forced expiratory flows at 25% (FEF25), and between 25% and 75% (FEF25–75) in boys and FEF25 in girls (In boys, for FEF25, −0.136 l/s, p = 0.008 in MPD and −0.153 l/s, p = 0.004 in HPD, respectively; for FEF25–75, −0.176 l/s, p = 0.013 in MPD and −0.167 l/s, p = 0.021 in HPD, respectively. In girls, for FEF25, −0.123 l/s, p = 0.043 in HPD), using LPD as the reference. Deficits in the annual growth rate of forced expiratory volume in 1 s (FEV1) were also negatively associated with air pollution in boys (−0.063 L, p = 0.032 in HPD).Conclusions: The study adds more evidence that exposure to air pollution has adverse effects on lung function growth in schoolchildren.

Clinical analysis of patients with pulmonary lymphangioleiomyomatosis (PLAM) in mainland China

Ling Ye, Meiling Jin, Chunxue Bai — 2010-06-07

Summary: Background and objective: There have been no clinical reports on pulmonary lymphangioleiomyomatosis (PLAM) based on large studies or epidemiological surveys in mainland China. The purpose of this study was to provide a retrospective analysis of PLAM patients in mainland China by reviewing the clinical data of PLAM cases reported.Methods: The China Academic Journals Full-text Database search engine was used to collect related cases in mainland China through the end of 2008. 120 cases met the study’s inclusion criteria and were reviewed for this analysis.Results: The average age of the 120 patients upon confirmed diagnosis was 37.3±6.4 years. The average duration from onset of symptoms to a confirmed diagnosis was 29.6±35.8 months, with 80 person-time patients having experienced misdiagnosis before the confirmed diagnosis. The major clinical manifestations of PLAM included progressive dyspnea, recurrent pneumatothorax, refractory chylothorax. Pulmonary function abnormalities included obstructive pulmonary ventilation disorders and degenerated diffusing capacity. Ten patients were found to be complicated with renal angiomyolipoma and 17 with abdominal or pelvic lymphangioleiomyoma. Half of the patients had undergone antiestrogen therapies such as progesterone, and four patients received pulmonary transplantation. The average duration from the confirmed diagnosis to death was 36.4±48.9 months among the 28 cases of death.Conclusions: Doctors in mainland China are becoming increasingly vigilant to PLAM, although misdiagnosis or missed diagnosis still exists. Provider attention to the correlation between PLAM and tuberous sclerosis complex, as well as to the possible involvement of multiple organs, is insufficient.

Distinct prognosis of idiopathic nonspecific interstitial pneumonia (NSIP) fulfilling criteria for undifferentiated connective tissue disease (UCTD)

2010-05-19

Summary: Background: Although idiopathic nonspecific interstitial pneumonia (NSIP) was initially identified as a provisional diagnosis, the 2008 American Thoracic Society Project concluded that idiopathic NSIP is a distinct form of idiopathic interstitial pneumonia. However, an association between idiopathic NSIP and autoimmune diseases still attracts interest. In this context, a recent study proposed an intriguing concept that idiopathic NSIP is the pulmonary manifestation of undifferentiated connective tissue disease (UCTD). However, this has not been confirmed in a large number of patients with idiopathic NSIP. The present study was conducted to investigate the proportion and characteristics of patients with idiopathic NSIP who meet the criteria for UCTD.Methods: We reviewed 47 consecutive patients with idiopathic NSIP and examined whether they met prespecified criteria for UCTD. Furthermore, we compared the clinical characteristics between patients fulfilling the UCTD criteria (UCTD-NSIP) and those not meeting them (Non-UCTD-NSIP).Results: Of 47 patients with idiopathic NSIP, 22 (47%) met the UCTD criteria. Common symptoms associated with connective tissue diseases (CTDs) were skin change (50%) and Raynaud’s phenomenon (41%) in UCTD-NSIP. UCTD-NSIP showed a female predominance and significantly higher percentages of lymphocytes with a lower CD4/CD8 ratio in bronchoalveolar lavage than Non-UCTD-NSIP. Interestingly, UCTD-NSIP had a significantly better survival than Non-UCTD-NSIP.Conclusions: Idiopathic NSIP included subjects who fulfilled the UCTD criteria, and these subjects had different clinical characteristics with significantly better outcome than those who did not meet the criteria. These data suggest that a part, but not all, of patients with idiopathic NSIP show CTD-like features with a distinct prognosis.

Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in idiopathic pulmonary fibrosis (IPF)

2010-05-19

Summary: Background: Experimental data have provided evidence that progenitor cells of bone marrow (BM) origin may play a role in the fibrogenic process of the lung.Objective: To probe the possible involvement of BM mesenchymal stem cells (MSCs) in the pathophysiology of Idiopathic Pulmonary Fibrosis (IPF) by investigating the molecular profile of these cells.Design: BM MSCs were studied in 10 IPF patients and 10 healthy controls. MSCs were identified by their immunophenotypic characteristics and their potential to differentiate towards adipocytes/osteocytes/chondrocytes. We evaluated the mRNA expression of genes involved in the lung injury of IPF, namely the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor beta-1 (TGF-β1) and the axis stromal-cell-derived factor-1 (SDF-1)/CXCR4 in BM MSCs using quantitative RT-PCR.Results: The BM MSCs of IPF patients displayed normal immunophenotypic characteristics and differentiation potential. No statistically significant difference was found between patients and controls in VEGF and FGF mRNA expression. TGF-β1 was not expressed in either patients or controls. A significant increase in SDF-1-TR1 and CXCR4 mRNA expression was detected in IPF patients (1.6 × 1025 ± 1.2 × 1025 and 3.1 × 107 ± 3.1 × 107, respectively) compared to controls (0.32 × 1025 ± 0.07 × 1025 and 1.67 × 107 ± 0.30 × 107, respectively) (p = 0.001 and p = 0.001, respectively) whereas SDF-1 levels in MSC supernatants were similar in patients and controls.Conclusions: The increased CXCR4 expression by patient MSCs suggests that the BM is probably implicated in the pathophysiology of IPF by mobilizing MSCs in response to or preceding lung injury. The potential role of BM MSCs in IPF is another interesting field for further investigation.

Spontaneous regression of thoracic malignancies

Toshita Kumar, Nick Patel, Arunabh Talwar — 2010-05-26

Summary: Background: Clinicians are frequently questioned by patients about the possibility of spontaneous regression of tumors. Although there are many reports and a few case series documenting spontaneous regression, there is concern that these cases may not represent true regression. Using specific criteria, we attempted to determine the incidence and types of thoracic malignancy most likely to regress spontaneously.Methods: We used a PubMed search of the phrase “spontaneous regression of thoracic lesions” reported from 1951 to December 2008. Using a modified Everson and Cole criterion we developed to define spontaneous regression, this search was refined for true spontaneous regression of primary and metastatic thoracic malignancies.Results: Only 5 cases in the literature involved spontaneous regression of a primary thoracic malignancy. These include pleural mesothelioma, primary lung cancer and adenoid cystic carcinoma. 71 cases involved true spontaneous regression of metastatic thoracic neoplasms, of which 5 cases showed regression of the primary extrapulmonary tumors along with the pulmonary metastasis. Thoracic metastasis from renal cell carcinoma was the most common malignancy found to regress spontaneously.Conclusion: Spontaneous regression of primary thoracic malignancy is rare. Renal cell carcinoma accounts for most reported cases.

Limited usefulness of QuantiFERON-TB Gold In-Tube® for monitoring anti-tuberculosis therapy

2010-06-10

Summary: The usefulness of IFN-γ release assays to monitor the efficacy of anti-tuberculosis (TB) treatment is controversial. Sixty patients affected by culture-confirmed pulmonary TB (M = 36; mean age: 39.2 yr; Italians = 28) were serially tested in a low prevalence setting by means of QuantiFERON-TB GOLD In-Tube (QFT-IT) at baseline and after a successful six-month therapy regimen (T6). A sub-group of 40 cases was also tested at 1 and 3 months. Overall, 88.3% of patients scored a QFT-IT positive result at baseline, with the higher proportion of TB-specific IFN-γ responses in foreign-born patients (p = 0.04). TB-specific responses were highly variable over time, the within-person variability being correlated with baseline IFN-γ levels (r = 0.731; p < 0.001). Overall, 61.6% of cases still tested QFT-IT positive at the completion of therapy. Average IFN-γ levels increased over time, being persistently significantly higher in Italian patients than in foreign-born cases both at baseline (p = 0.03) and at T6 (p = 0.02). Reversion mainly occurred in patients (26.6%) with baseline IFN-γ levels close to the conventional cut-off value. No indeterminate results were recorded at any study time point.In conclusion, QFT-IT adds no significant information to clinicians for treatment monitoring when applied in routine clinical practice in a low prevalence setting. Kinetics of T cell responses upon TB treatment and reversion (and conversion) thresholds need to be addressed. Diversity of IFN-γ responses among patients of different geographic origin is an issue to be investigated further.

Effects of interval exercise training on respiratory drive in patients with chronic heart failure

2010-07-22

Summary: Background: Patients with chronic heart failure (CHF) suffer from ventilatory abnormalities. This study examined the effects of interval exercise training on the respiratory drive in CHF patients.Methods: Forty-six clinically stable CHF patients (38 males/8 women, mean age = 53 ± 11 years) participated in an exercise rehabilitation program (ERP) 3 times/week, for 12 weeks by interval training modality with or without the addition of resistance training. All patients underwent symptom-limited cardiopulmonary exercise testing (CPET), and measurements of mouth occlusion pressure at 100 ms (P0.1) and maximum inspiratory muscle strength (PImax) before and after ERP. Respiratory drive was estimated by mouth occlusion pressure P0.1 and P0.1/PImax ratio at rest, and the ventilatory pattern by resting mean inspiratory flow (VT/TI) and by VT/TI at identical CPET workloads, before and after ERP. We also studied a control non exercising group of 11 patients (8 men and 3 women).Results: P0.1 at rest decreased from 3.04 ± 1.52 to 2.62 ± 0.9 cmH2O (p = 0.015), P0.1/PImax % at rest from 4.56 ± 3.73 to 3.69 ± 2.03 (p = 0.006), resting VT/TI from 0.44 ± 0.10 to 0.41 ± 0.10 l/s (p = 0.014), and VT/TI at identical work rate from 2.13 ± 0.59 to 1.93 ± 0.58 l/s (p = 0.001) after ERP. VO2 at peak exercise increased from 16.3 ± 4.8 to 18.5 ± 5.3 ml/kg/min (p < 0.001) in the exercise group. No improvement was noted in the control group.Conclusions: ERP by interval training improves the respiratory drive and ventilatory pattern at rest and during exercise in CHF patients.

Is there an alternative to pre-flight hypoxic challenge testing in scoliotic patients?

Debrata Bandyopadhyay, Nicholas S. Oscroft, John M. Shneerson, Ian E. Smith — 2010-06-07

Summary: Introduction: Hypoxic challenge testing (HCT) is not readily available in all hospitals. It has recently been shown that resting oximetry does not reliably predict the results of HCT in patients with extrapulmonary restrictive lung disease. We assessed other clinical tests to see if they might be used as an alternative screen for HCT.Methods: People with primary thoracic scoliosis were recruited. Resting SpO2, arterial blood gases (ABG’s), lung function and shuttle walking test (SWT) were measured. All subjects underwent HCT breathing an inhaled oxygen fraction of 15% for 20 min, or until SpO2 fell below 85%, when ABG’s were taken.Results: Fourteen people (5 male) with thoracic scoliosis, Cobb angle 93 (31)°, aged 65 (8.5) years, FEV1 0.86 (0.4) L, FVC 1.2 (0.4)L were studied. The resting SpO2 was 96 (2) %, PaO2 9.2 (1) kPa and PaCO2 6.1 (0.4) kPa. HCT was positive in 11 subjects (PaO2 <6.6 kPa). Eight of 11 HCT positive subjects had a resting SpO2 > 95%. Positive correlation was found between SpO2 at SWT termination and PaO2 following HCT (r = 0.56, p = 0.02). Those with saturations of 92% or under at SWT termination had positive HCT.Conclusions: Despite normal resting SpO2 subjects with thoracic scoliosis may have positive HCT. Current recommendations for air travel do not accurately identify these people. Desaturation following a SWT may provide a useful screening tool, however a low threshold for performing HCT on people with thoracic scoliosis prior to air travel is warranted.

Continuous positive airway pressure therapy improves arterial elasticity in patients with obstructive sleep apnea

2010-05-31

Summary: Background: Reduced arterial elasticity is an important mediator of accelerated atherogenesis and consequent increased cardiovascular morbidity in obstructive sleep apnea (OSA). The aim of our study was to investigate whether continuous positive airway pressure (CPAP) therapy may improve arterial elasticity in subjects with OSA.Methods: In 44 subjects with OSA, we measured arterial elasticity by applanation tonometry before and after 6 months of treatment with CPAP. Nine OSA+ subjects withdrew from the study.Results: The 35 patients with OSA who completed the 6-month CPAP treatment showed a marked reduction in both the large artery (LAEI, P=0.001) and small artery (SAEI, P=0.009) elasticity indices, independent of potential confounders. In OSA+ subjects who withdrew from the study, SAEI and LAEI did not change significantly over time.Conclusions: Six months of CPAP therapy improves arterial elasticity in subjects with OSA.

Unified disease, unified management: Treating allergic rhinitis and asthma with nasally inhaled corticosteroid

2010-07-16

Summary: Persistent allergic rhinitis (AR) and asthma constitute a common comorbidity. Combined treatment is recommended by prescribing intranasal plus oral inhaled corticosteroids.This study was carried out to assess the efficacy of an alternative regimen to treat this condition.All recruited patients suffered from persistent AR and asthma. Diagnosis and classification of AR and asthma were based on international guidelines. The experimental group received fluticasone propionate (FP), 500μg/day during six weeks, inhaled exclusively through the nose using a valved large volume spacer attached to a facemask. The comparison group also received the same dose of orally inhaled FP, during the same time period, plus intranasal aqueous fluticasone, 200μg/day. There were no statistical differences between both groups regarding AR and asthma severity, clinical scores, acoustic rhinometry, lung function, and FeNO upon admission and during the follow up period. Intragroup analysis demonstrated a significant improvement for allergic rhinitis and asthma scores as well as for FeNO from admission to the sixth week (p<0.01) in both groups.Results suggest that exclusive nasally inhaled fluticasone propionate should be considered as an alternative step in the management of patients suffering from AR and asthma comorbidity.

CRP: Body composition and other factors

Viroj Wiwanitkit — 2010-06-07

I read the recent report on C-reactive protein (CRP) by Jung et al. with a great interest. Jung et al. detected that the coexistence of high fat accumulation and increased CRP level presented a relationship with pulmonary function. Indeed, there are many other factors that can lead to the proposed relationship. Jung et al. cross published another paper that the menstruation status and menopause was also relating to the CRP level. It should be notified that CRP is only a non specific blood test in laboratory medicine and many factors can lead to the aberration of its level. To study a relationship between CRP level and any physiological or pathological condition by a single factor or few factors analysis might have problems on omitting of other excluded factors.