Noel Lampron

Effects of Bronchial Thermoplasty on Airway Smooth Muscle and Collagen Deposition in Asthma

RATIONALE The aim of bronchial thermoplasty is to improve asthma symptoms by reducing central airway smooth muscle mass. Up to now, the reduction of smooth muscle mass has been documented for only 1 group of 10 patients who had 15% or more of their pretreatment total bronchial biopsy area occupied by smooth muscle. OBJECTIVES To evaluate the effects of bronchial thermoplasty on airway smooth muscle mass and airway collagen deposition in adult patients with asthma, regardless of pretreatment smooth muscle area. METHODS Seventeen patients with asthma underwent bronchial thermoplasty over the course of three visits. At Visit 1, bronchial biopsies were taken from the lower lobe that was not treated during this session. At Visit 2 (3-14 wk after the first visit), all 17 patients underwent biopsy of the lower lobe treated during the first procedure. At Visit 3 (7-22 wk after the first visit), nine patients agreed to undergo biopsy of the same lower lobe. Histological and immunohistochemical analyses were performed on the biopsy specimens. MEASUREMENTS AND MAIN RESULTS Bronchial thermoplasty decreased airway smooth muscle from 12.9 ± 1.2% of the total biopsy surface at Visit 1 to 4.6 ± 0.8% at Visit 2 (P < 0.0001). For the nine patients who underwent a third biopsy, mean airway smooth muscle area was 5.3 ± 1.3% at Visit 3 (P = 0.0008 compared with baseline). Bronchial thermoplasty also decreased Type I collagen deposition underneath the basement membrane from 6.8 ± 0.3 μm at Visit 1 to 4.3 ± 0.2 μm at Visit 2 (P < 0.0001) and to 4.4 ± 0.4 μm for nine patients at Visit 3 (P < 0.0001 compared with baseline). Over the course of 1 year after treatment, the doses of inhaled corticosteroid, the number of severe exacerbations, and asthma control all improved (P ≤ 0.02). CONCLUSIONS For patients with severe asthma, bronchial thermoplasty reduced the smooth muscle mass of treated airway segments, regardless of the baseline level of muscle mass. Treatment also altered the deposition of collagen. At follow-up, bronchial thermoplasty improved asthma control; however, the limited number of subjects did not allow us to evaluate possible correlations between these improvements and the studied histological parameters. Further studies are needed to confirm these results and evaluate their persistence.

Influence of natural antigenic exposure on bronchoalveolar lavage in subjects with pollen-induced rhinitis

To determine if atopic subjects without asthma naturally exposed to antigens to which they are sensitized demonstrate evidence of lower airway inflammation, we studied 10 subjects with recurrent seasonal allergic rhinitis to pollens. Each subject had a monthly methacholine challenge and two bronchoalveolar lavages (BAL), one during symptoms of allergic rhinitis and one out of season. The percentage of macrophages, lymphocytes, neutrophils, eosinophils, and mast cells in the lavage fluid were determined on Diff-Quik, nonspecific esterase, or toluidine blue-stained cytocentrifuge preparations. The total number of cells recovered on BAL was 23.2 +/- 3.5 X 10(6) (mean +/- SEM) (13.3 +/- 2.3 X 10(4) cells per milliliter) in season, during symptoms of allergic rhinitis, and 33.8 +/- 7.4 X 10(6) (15.2 +/- 3.1 X 10(4) cells per milliliter) out of season (p greater than 0.05). BAL cell-differential counts (percent) in/out season were similar for macrophages (89.0/84.6), lymphocytes (9.1/12.8), neutrophils (1.3/2.1), eosinophils (0.5/0.5), epithelial cells (0.37/0.46), and mast cells (0.0008/0.0013). Blood eosinophil counts, taken, respectively, in and out of season, were 135.5 +/- 26.8 X 10(6)/L and 102.8 +/- 20.6 X 10(6)/L (p greater than 0.05). Although overall airway responsiveness increased slightly during the pollen season, it did not reach statistical significance (geometric mean of provocative concentration causing a 20% fall in FEV1 [milligrams per milliliter], 98.8 during antigenic exposure compared to 121.4 out of season) (p greater than 0.05. These observations suggest that in subjects without asthma, no changes in cell differential are detected on BAL at the time of maximal symptoms of allergic rhinitis.

Randomized Trial Comparing Patient Comfort Between the Oral and Nasal Insertion Routes for Linear Endobronchial Ultrasound.

Background:Linear endobronchial ultrasound (EBUS) is a safe and accurate sampling method for mediastinal adenopathy. The transnasal approach has been proposed to improve patient comfort, but no data compare the oral and nasal routes. The objective was to compare patient comfort during linear EBUS under conscious sedation between the oral and the nasal routes. Methods:An open-label randomized study comparing the 2 insertion routes for linear EBUS was conducted. Standardized protocols for sedation and topical anesthesia were used. Primary outcome was subjects’ comfort measured by a 10-point scale filled 2 hours after the procedure. Willingness to return for a repeat examination, procedural characteristics, complications, and diagnostic yields were also compared. Results:A total of 220 subjects were randomized and allocated to the nasal (n=110) or oral (n=110) route. Twenty-seven subjects in the nasal group (24.5%) had a failed nasal insertion but were analyzed in the nasal group. Procedural characteristics were similar (EBUS duration, doses of sedatives and lidocaine, number of stations sampled, complications). There was no difference between the nasal and oral groups in subjects’ comfort (8.3 vs. 8.3, respectively, P=0.99), overall patient satisfaction (8.9 vs. 9.1, respectively, P=0.34), subjects’ willingness to return (96% vs. 97%, P=1.00), and physician-reported subject comfort. Rates of adequate specimens and diagnostic yields did not differ significantly between the groups. Conclusions:For linear EBUS, the nasal and oral approaches confer a similarly high degree of patient comfort with similar complication rates and diagnostic yield. Patient and physician preferences should dictate the route of insertion.

Influence of trainee involvement on procedural characteristics for linear endobronchial ultrasound

Linear endobronchial ultrasound (EBUS) is a safe and effective method for the diagnostic sampling of mediastinal lymph nodes. However, there is a learning curve associated with the procedure and operator experience influences diagnostic yield. We sought to determine if trainee involvement during EBUS influences procedural characteristics, complication rate, and diagnostic yield.

Evaluation of Pulmonary Nodules Using the Spyglass Direct Visualization System Combined With Radial Endobronchial Ultrasound: A Clinical Feasibility Study

Background: Sampling of peripheral pulmonary nodules with radial endobronchial ultrasound (p-EBUS) increases diagnostic yield of bronchoscopy. However, diagnostic yield is influenced by numerous factors. Objective: We evaluated the use of SpyGlass, a one millimeter diameter optic fiber, to obtain images of the distal mucosa and of pulmonary lesions detected with p-EBUS to determine if visual aspect of the distal mucosa was predictive of diagnosis. Methods: We prospectively recruited subjects investigated for peripheral nodules. Bronchoscopy was performed and p-EBUS was used to locate the lesion through a guide sheath. The Spyglass fiber was introduced in the sheath to obtain images of the distal bronchial mucosa. Tissue sampling was subsequently done. Results: Fifteen patients were enrolled in the study. A final diagnosis of malignancy was confirmed in 80%. All lesions could be located using p-EBUS (100%). Diagnostic sensitivity for p-EBUS was 58.3%. Distal mucosa could be imaged with SpyGlass in 14/15 patients (93.3%). Mucosal appearance was described as abnormal in 7 out of the 15 subjects. Mean SpyGlass procedure time was 6.5 minutes. No direct complication was reported. Conclusion: Spyglass can be used in combination with p-EBUS to obtain images of the distal bronchial mucosa and peripheral pulmonary nodules. More patients will be needed to confirm whether mucosal appearance can be predictive of malignancy.

The Unsettled Question of Brochodilator Aerosol Administration in Mechanically Ventilated Patients

Aerosols have gained wide acceptance over the past 10 years for the treatment of obstructive diseases. However, much controversy still exists about their use and mode of administration in the setting of intensive care units for intubated patients. The current literature was reviewed addressing the following question: In intubated and mechanically ventilated patients with airway obstruction, should bronchodilator aerosols be delivered through a metered-dose inhaler (MDI) or a nebulizer in order to reduce complications associated with high airway resistance? Most often investigators have examined, in uncontrolled trials, the effect of bronchodilator aerosols administered either through MDIs or nebulizers in lung models, or in populations of patients with heterogeneous conditions. An extremely wide range of bronchodilator dosages has been studied. Clinical outcomes have consisted of either drug deposition or lung mechanical characteristics. Only three randomized controlled trials comparing the effects of bronchodilator aerosols delivered through a nebulizer to those delivered through an MDI have been published, without clearly demonstrating the superiority of one mode of administration over the other. There is a need for randomized controlled trials comparing the effect of bronchodilator aerosols delivered through nebulizer versus MDI on the incidence of ventilator-associated complications in mechanically ventilated patients with obstructive lung diseases.