Home-based respiratory rehabilitation in adult patients with moderate or severe persistent asthma.

OBJECTIVE: We assessed retrospectively the feasibility of a home-based respiratory rehabilitation (RR) program for asthmatics under optimal pharmacological treatment, as this type of care can reduce costs and offer a more patient-friendly approach for subjects with persistent asthma. METHODS: Fifty-two patients with persistent asthma were recruited to the RR program (20 males, 32 females, 54 ± 11 (SD) years, forced expiratory volume in one second 71 ± 33% of predicted mean value, BMI 29.9 ± 7.9 kg/m(2)). This two-month protocol comprised education sessions, respiratory physiotherapy and an exercise training program at home and in groups supervised by an adapted physical activity instructor. RESULTS: Thirty-nine patients completed the whole RR program, i.e. 25% dropout. The dropout rate was significantly higher with respect to younger patients in employment. The number of exacerbations decreased significantly during the year following the program, regardless of whether the patients had dropped out (p < 0.02) or not (p < 0.001). The distance walked during a 6-min walking test increased by 33 m (p < 0.001). Several indices measured during a cycle ergometer test increased significantly after RR: peak oxygen uptake (10%), oxygen uptake at ventilatory threshold (12%) and maximum load (19%), all at a similar maximum heart rate. Concerning quality of life assessment, the Short-Form-36 Item Health Survey revealed a non-significant improvement in the "health change" item after RR (p < 0.07). CONCLUSIONS: This study demonstrates the potential of a home-based program in the treatment and rehabilitation of patients with asthma. Both functional and physiologic indices improved during the follow-up period.

Increased asymptomatic airway hyper-responsiveness in obese individuals.

OBJECTIVE: Asymptomatic airway hyper-responsiveness (AHR) represents a risk of further accelerated decline in lung function, and of asthma. Due to the fact that rare and contradictory results exist concerning the impact of obesity on BHR, we re-assessed the prevalence of bronchial hyper-responsiveness (BHR) in a large cohort of 60 lean, 84 overweight, and 360 class 1-3 obese non-asthmatic individuals, by coupled plethysmography and spirometry. METHODS: Baseline-specific airway conductance (SGaw) and spirometric values were measured and then a methacholine challenge testing (MCT) was performed and considered as positive when a ≥200% increase in specific airway resistance (SRaw = 1/SGaw) was reached. RESULTS: Compared to lean and overweight subjects, obese subjects of any class presented about a twice more frequent AHR (∼ 50% in obese vs. 17 and 26% in lean and overweight subjects, respectively). However, the bronchial sensitivity (methacholine dose doubling SRaw) and the shape of the relationship between SGaw and cumulative methacholine doses were the same in the five groups of individuals. CONCLUSION: The present data show a more frequent AHR in obese subjects. The association of plethysmography with spirometry, by taking into account the bronchodilator effect of the lung inflation (preceding the expiratory flow measurement) in some individuals, permitted to include some MCT which would have been otherwise excluded.

Spirometry centile charts for young Caucasian children: the Asthma UK Collaborative Initiative.

RATIONALE: Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. OBJECTIVES: We aimed to build on previous models by collating existing reference data in young children (aged 3-7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. METHODS: The Asthma UK Collaborative Initiative was established to collate lung function data from healthy young children aged 3 to 7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (lambda, micro, sigma) method and extend previously published equations down to 3 years of age. MEASUREMENTS AND MAIN RESULTS: The Asthma UK centile charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated data set reflects a variety of equipment, measurement protocols, and population characteristics and may be generalizable across different populations. CONCLUSIONS: We present prediction equations for spirometry for preschool children and provide a foundation that will facilitate continued updating.

Physiological, histological and biochemical properties of rat skeletal muscles in response to hindlimb suspension.

In previous study, we found that the reduced exercise-induced production of reactive oxygen species (ROS) reported in slow-oxidative muscle of hypoxemic rats and also in chronic hypoxemic patients did not simply result from deconditioning. In control rats and after a 3-week period of hindlimb suspension (HS), the slow-oxidative (Soleus, SOL) and fast-glycolytic skeletal muscles (Extensor digitorum longus, EDL) were sampled. We determined the response to direct muscle stimulation (twitch stimulation (TS), Maximal force (Fmax)), twitch amplitude and maximal relaxation rate, tetanic frequency, endurance to fatigue after muscle stimulation (MS), the different fibre types based on their myofibrillar adenosinetriphosphatase (ATPase) activity, and the intra-muscular redox status (Thiobarbituric Acid Reactive Sustances: TBARS, reduced glutathione: GSH, reduced ascorbic acid: RAA). After the 3-w HS period: (1) the contractile properties were modified in SOL only (reduced Fmax and twitch amplitude, increased tetanic frequency); (2) the fibre typology was modified in both muscles (in SOL: increased proportion of IIa and IIc fibres, in EDL: increased proportion of IId/x fibres but decreased proportion of IIb fibres); and (3) only in SOL, the TBARS level increased and the GSH and RAA concentrations decreased at rest and after fatiguing MS. Thus, HS accentuates the exercise-induced ROS production in slow-oxidative muscle in a direction opposite to that measured in chronic hypoxemic rats. This strongly suggests that hypoxemia reduces the ROS production independently from any muscle disuse.

T regulatory cells in stable posttransplant bronchiolitis obliterans syndrome.

BACKGROUND: Obliterative bronchiolitis (OB), mainly mediated by T cells, remains the major cause of morbidity and death in long-term lung transplant. Acute rejection (AR), also a T-cell mediated process, is strongly linked to OB. For unknown reasons, several patients with OB halt their pulmonary function decline and stabilize their obstructive defect for a long period. Our aim was to assess the T-cell activation in blood, induced sputum, and broncho-alveolar lavage during AR, stable OB (sOB), and evolving OB (eOB). METHODS: T-cell phenotype and cytokine production were assessed by flow cytometry in these three compartments. Interleukin-4, interferon-gamma and transforming growth factor (TGF)-beta levels were measured by enzyme-linked immunosorbent assay in blood cell culture supernatants. Results were compared between healthy lung transplant recipients and AR (n=7), sOB (n=7), and eOB (n=13). RESULTS: Stable and evolutive OB were characterized by a Treg, Th1, and Th2 activation, but compared to eOB, Treg and Th2 cells predominated in sOB. A clear Th1 activation was observed in AR. TGF-beta was increased in AR and evolving OB. CONCLUSION: These preliminary results indicate a contrasted T-cell activation profile depending on the clinical conditions. We speculate that Treg cells could counterbalance the Th0 activation seen in evolving OB and participate in stabilization of airway obstruction.

Pulmonary function tests as a predictor of quantitative and qualitative outcomes after thoracic surgery for lung cancer.

BACKGROUND: Pulmonary function tests are used to select patients with non-small-cell lung cancer (NSCLC) suitable for thoracic surgery. We studied the impact of pulmonary function tests on both quantitative (morbidity, mortality, and overall survival [OS]) and qualitative (quality of life [QOL]) outcomes of patients undergoing thoracic surgery for NSCLC. PATIENTS AND METHODS: Patients with proven or highly probable NSCLC referred for thoracic surgery were eligible. The postoperative outcomes morbidity, 90-day mortality, OS, and QOL based on PGWBI and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 were studied according to the results of the preoperative pulmonary function tests (forced expiratory volume in 1 second [FEV(1)]; vital capacity, residual volume, total lung capacity, airways resistance, diffusing capacity corrected for alveolar volume). RESULTS: A total of 110 patients were studied, with 94 patients eligible for analysis. Postoperative mortality and morbidity affected 9.5% and 40% of patients, respectively. These patients presented with significantly lower preoperative values of vital capacity, total lung capacity, and diffusing capacity corrected for alveolar volume and higher preoperative values of airways resistance compared with patients with an uncomplicated postoperative course. Better survival was correlated with higher preoperative values of FEV(1), vital capacity, total lung capacity, and a lower pulmonary distension, especially when expressed as a percentage of predicted value. None of the postoperative QOL scores was influenced by preoperative pulmonary function tests results. CONCLUSION: Pulmonary function tests allow a relatively good prediction of postoperative quantitative outcomes such as postoperative morbidity and mortality as well as OS after thoracic surgery for NSCLC. However, pulmonary function tests remain poorly correlated to postoperative qualitative outcomes, making QOL a separate and essential assessment of the health status of patients with resected NSCLC.

Upregulation of chemokines in bronchoalveolar lavage fluid as a predictive marker of post-transplant airway obliteration.

BACKGROUND: The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB. METHODS: Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 +/- 164 days and 307 +/- 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 +/- 323 and 152 +/- 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups. CONCLUSIONS: These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.

Depressed fatigue-induced oxidative stress in chronic hypoxemic humans and rats.

It was already documented that acute hypoxemia reduces the oxidative stress following static as well as dynamic handgrip bouts in humans. Then, we examined if chronic hypoxemia could produce the same effect in patients suffering from chronic respiratory insufficiency. In rats, we studied the respective consequence of a one-month exposure to normobaric hypoxia on two muscles (soleus, SOL, and extensor digitorum longus, EDL) which have high and low aerobic metabolism, respectively. Compared to healthy humans, the resting level of erythrocyte reduced glutathione (GSH) was significantly lower in chronic hypoxemic patients, and after a handgrip contraction sustained at 50% of maximal until exhaustion the GSH level and plasma thiobarbituric acid reactive substances (TBARS) did not vary. A 20-min period of oxygen supplementation partly restored the post-handgrip oxidative stress. Compared to control rats, SOL muscle of hypoxemic animals had lower intra-muscular resting level of GSH; after a 3-min muscle stimulation (MS) leading to fatigue, TBARS did not vary in SOL and EDL and the GSH decrease was absent in SOL whereas it persisted in EDL. We concluded that chronic hypoxemia depressed the fatigue-induced oxidative stress, the effects prevailing in muscles having a high oxygen demand.

Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients.

OBJECTIVE: Bronchoalveolar lavage (BAL) fluid provides a crucial tool for investigation of the cellular component of the deep lung spaces and hence to approach the alloreactive response following lung transplantation. This study investigated whether BAL cell profiles can assist for the diagnosis of certain postoperative complications. METHODS: We conducted a retrospective analysis of both transbronchial biopsy and bronchoalveolar lavage materials in a series of 26 consecutive lung transplant recipients (LTR) in relationship with their clinical status at the time of the procedure. BAL fluid was subjected to cell morphology as well as flow cytometric phenotypic analyses. The samples were labeled as follows: normal transplant in clinically stable and healthy recipients, n=58; acute rejection (AR), n=58; infection (INF), n=31; and obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS) n=27. RESULTS: Total BAL cell counts were the highest in INF. Lymphocytic alveolitis was suggestive of both acute allograft rejection and CMV viral infection, with a combined significant increased HLA-DR positive cells in AR. Alveolar neutrophilia with an increased CD4/CD8 ratio was correlated with the diagnosis of OB. The neutrophil percentages, HLA-DR and CD57 positive cells were significantly higher when an infection was present. CONCLUSION: These findings suggest that BAL cell analysis could give complementary information of histological data and further insight into immunologic events after lung allograft. A longitudinal surveillance of BAL cell profiles in an individual patient may be suggestive for a preclinical state of posttransplant acute rejection, bacterial infection and obliterative bronchiolitis.

One-year occupational exposure to a cold environment alters lung function.

Numerous observations have shown that breathing cold air causes bronchospasm and increases respiratory tract secretions in asthmatic patients and normal individuals. However, few studies have been conducted on the respiratory effects of protracted daily exposures to a cold environment. In this 1-yr study, the authors examined individuals who spent 6 hr a day in cold stores (+3 degrees C to + 10 degrees C) and spent approximately 25% of that time at +3 degrees C. The protocol included a questionnaire about clinical symptoms, with measurements of baseline pulmonary function and airway responses to carbachol and to nasal inhalation of cold air (-5 degrees C). Eleven subjects were examined prior to their first occupational exposure to cold, and again following 6 mo and 12 mo of work in the cold environment. Compared with a control group of 6 subjects engaged at the same time but who did not work in cold stores, 6 of 11 individuals who worked 12 mo in a cold environment experienced increased symptoms of rhinitis, sore throat, and cough. Physiological measurements at 6 mo and 12 mo showed a progressive decrease in forced expiratory volume in 1 sec and a progressive increase in the baseline value of central airway resistance. Forced expiratory flow measured between 25% and 75% of vital capacity had decreased at 6 mo, but showed no further change at 12 mo. A progressive enhancement of bronchial reactivity to carbachol was noted at 6 mo and again at 12 mo, but airway response to nasal breathing of cold air did not vary. The authors concluded that 1 yr of daily exposure to a cold occupational environment elicits a modest--but significant--airflow limitation, accompanied by bronchial hyperresponsiveness, with the effects beginning within 6 mo of exposure.

A retrospective study of silicone stent placement for management of anastomotic airway complications in lung transplant recipients: short- and long-term outcomes.

BACKGROUND: Airway anastomotic complications remain a major cause of morbidity and mortality after lung transplantation (LT). Few data are available with regard to the use of silicone stents for these airway disorders. The aim of this retrospective study was to evaluate the clinical efficacy and safety of silicone stents for such an indication. METHODS: Data of adult lung transplant recipients who had procedures performed between January 1997 and December 2007 at our institution were reviewed retrospectively. We included patients with post-transplant airway complications who required bronchoscopic intervention with a silicone stent. RESULTS: In 17 of 117 (14.5%) LT recipients, silicone stents were inserted at a mean time of 165 (range 5 to 360) days after surgery in order to palliate 23 anastomotic airway stenoses. Symptomatic improvement was noted in all patients, and mean forced expiratory volume in 1 second (FEV(1)) increased by 672 +/- 496 ml (p < 0.001) after stent insertion. The stent-related complication rate was 0.13/patient per month. The latter consisted of obstructive granulomas (n = 10), mucus plugging (n = 7) and migration (n = 7), which were of mild to moderate severity and were successfully managed endoscopically. Mean stent duration was 266 days (range 24 to 1,407 days). Successful stent removal was achieved in 16 of 23 cases (69.5%) without recurrence of stenosis. Overall survival was similar in patients with and without airway complications (p = 0.36). CONCLUSIONS: Silicone stents allow clinical and lung function improvement in patients with LT-related airway complications. Stent-related complications were of mild to moderate severity, and were appropriately managed endoscopically. Permanent resolution of airway stenosis was obtained in most patients, allowing definitive stent removal without recurrence.

Comparison of induced sputum and bronchoalveolar lavage in lung transplant recipients.

BACKGROUND: Chronic lung rejection is characterized by obliterative bronchiolitis (OB) diagnosed based on spirometric criteria reflecting an already advanced process. Biologic markers such as bronchoalveolar lavage (BAL) neutrophilia or increased levels of chemokines (interleukin-8, RANTES [regulated on activation: normal T cell expressed and secreted]) have been proposed as early diagnosis tools. However, BAL is too invasive to be used as a routine strategy. Induced sputum (IS), however, is a non-invasive method of recovering bronchial cells. METHODS: The aim of this study was to compare BAL and IS differential cellular counts as well as IL-8 and RANTES levels between patients with bronchiolitis obliterans syndrome (BOS), recipients with good outcome and well-preserved lung function (non-BOS) and non-transplanted controls. We compared 34 BAL and IS findings obtained consecutively from 34 lung transplant recipients (LTRs), including 22 non-BOS and 12 BOS patients. RESULTS: IS results were compared with 19 samples from non-transplanted controls. IS was well tolerated. There was no correlation between BAL and sputum cell populations. BAL neutrophils and IL-8 levels were increased in BOS, and these parameters were positively correlated. Moreover, BAL neutrophils and IL-8 levels were both negatively correlated with respiratory function. Sputum evaluation allows discrimination of BOS from non-BOS by the presence of higher neutrophil and eosinophil counts. Moreover, IS neutrophils and eosinophils were both correlated with lung function parameters. In contrast to BAL, IL-8 level in sputum was not a useful predictive marker of BOS development. IS RANTES levels were higher in BOS than in healthy recipients and correlated significantly with IS eosinophils. CONCLUSIONS: IS and BAL provide different but complementary data. In this study, IS appeared to be a useful, non-invasive tool for LTR monitoring. Furthermore, IS provides new insights into BOS pathogenesis, especially with regard to implication of eosinophils and its chemokine, RANTES, at the bronchial level.

Matched adaptations of electrophysiological, physiological, and histological properties of skeletal muscles in response to chronic hypoxia.

This study tried to differentiate the consequences of chronic hypoxia on the electrophysiological and physiological properties and the histological characteristics of slow and fast muscles in rats. Animals inhaled a 10% O(2) concentration for a 1-month period. Then, slow [soleus (SOL)] and fast [extensor digitorum longus (EDL)] muscles were analyzed in vitro by physiological and electrophysiological measurements and histological analyses. The results were compared to those obtained in corresponding muscles of an age-matched normoxic group. After exposure to hypoxia: (1) in SOL, there was a tendency to elevated F(max), a significant increase in twitch force and tetanic frequency and a shortening of M-wave duration, and a reduced percentage of type I fibres, whereas the proportion of type IIa fibres doubled; (2) in EDL, F(max) and tetanic frequency were lowered, the muscle became less resistant to fatigue, and the proportion of type IId/x fibres was halved. Then, after 1 month of hypoxia, in the SOL muscle, both the contractile and histological properties resemble those of a fast muscle. By contrast, the EDL became slower, despite its histology was modestly affected. Reduced muscle use in hypoxia could explain the tendency for deteriorating adaptations in EDL, and the faster properties of SOL could result from hypoxia-induced inhibition of the growth-related fast-to-slow shift in muscle fibre types.

Right-to-left atrial shunt without pulmonary artery hypertension.

A 70-year-old woman without any history of pulmonary or cardiac disease developed breathlessness with severe arterial hypoxemia. Cardiac ultrasound examination and spirometry were normal. Cardiac catheterization and intravenous microbubble injection demonstrated an interatrial right-to-left shunt. The defect was closed surgically, and the patient recovered immediately. On surgery, the aorta was elongated, inducing an angulation of the interatrial septum and leading to the atrial septal defect just above the inferior vena cava.