Small airway disease in asthma and COPD: clinical implications.

Asthma and COPD have a high personal, societal, and economic impact. Both diseases are characterized by airway obstruction and an inflammatory process. The inflammatory process affects the whole respiratory tract, from central to peripheral airways that are <2 mm in internal diameter, the so-called small airways. There is an increased interest in small airway disease, and some new insights have been gained about the contribution of these small airways to the clinical expression of asthma and COPD, as reviewed in this article. Newly developed devices enable drugs to target the small airways, and this may have implications for treatment of patients with asthma, particularly those not responding to large-particle inhaled corticosteroids or those with uncontrollable asthma. The first studies in COPD are promising, and results from new studies are eagerly awaited.

[A man with persistent wheezing and haemoptysis]. / Een man met piepende ademhaling en hemoptoë.

A 33-year-old man with wheezing and haemoptysis was evaluated at the emergency department. At physical examination, diminished breathing was heard over the left lung. Two X-rays were made, an inspiratory and an expiratory one. The expiratory X-ray showed signs of an obstruction of the left main bronchus. The cause was a carcinoïd.

Determinants of overweight and obesity in lung transplant recipients.

BACKGROUND: Obesity-related diseases have been shown to affect post-lung transplantation survival. An estimated 30% of lung transplant recipients develop overweight. OBJECTIVE: The aim of this study was to examine the possible determinants of large increases in weight after lung transplantation. The contribution of physical activity, food intake, and resting energy expenditure was examined in lung transplant recipients. METHODS: In this cross-sectional study 21 overweight lung transplant recipients (11 men, mean age 57 ± 7 years; BMI 30 ± 3) and 21 normal-weight lung transplant recipients (11 men, mean age 56 ± 5 years; BMI 22 ± 3) were matched for disease, gender, age, prescribed medication, and time since lung transplantation. Physical activity was measured by a pedometer and a questionnaire; resting energy expenditure was measured by the ventilated-hood technique, and daily food intake by a dietician. Additionally, fat-free mass, lower-body strength, and fatigue were measured. RESULTS: The overweight lung transplant recipients had a significantly lower number of steps per day (4,686 ± 3,266 vs. 7,524 ± 3,448 steps/day, p = 0.01) and a lower fat-free mass (64 ± 9 vs. 75 ± 6%, p < 0.05) compared to normal-weight recipients. Obese subjects had a lower percentage of predicted resting energy expenditure level compared to normal-weight recipients (90 ± 14 vs. 100 ± 14% predicted, p = 0.04). CONCLUSION: Our data suggest that overweight in lung transplant recipients is associated with a lower fat-free mass and lower levels of physical activity and resting energy expenditure compared to normal-weight recipients.

Asthma in patients climbing to high and extreme altitudes in the Tibetan Everest region.

OBJECTIVES: The aim of this study was to investigate the behavior of asthma in patients traveling to high and extreme altitudes. METHODS: Twenty-four Dutch patients with mild asthma did a trekking at high and extreme altitudes (up to 6410 m = 21030 ft) in the Tibetan Everest region. Asthma symptoms, use of asthma medication, symptoms of acute mountain sickness, spirometry, peripheral oxygen saturation, and heart rate were measured at 1300 m (baseline), and at 3875, 4310, 5175, and 6410 m. Asthma symptoms were assessed by means of a modified version of the Asthma Control Test. Symptoms of acute mountain sickness were scored by the Lake Louise self-report questionnaire. The expedition staff, consisting of seven healthy persons, acted as a control group. RESULTS: In both asthmatics and controls, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) decreased with increasing altitude, whereas FEV1 as percent of FVC (FEV1%FVC) did not change. In both groups, peak expiratory flow (PEF) increased with increasing altitude. In general, differences in spirometric values between asthmatics and controls were not significant. Asthma symptoms did not change with increasing altitude. During ascent, less than half of the asthma patients increased their medication use. According to the Lake Louise score, no acute mountain sickness occurred, except for in the asthma group at 6410 m, which showed mild acute mountain sickness at that altitude. As expected, peripheral oxygen saturation decreased with increasing altitude in asthmatics and controls, differences between the two groups not being significant. In general, heart rate (at rest) did not change with altitude, except for an increase in asthmatics at 6410 m. CONCLUSIONS: These results suggest that traveling to high and extreme altitudes is safe for patients with mild asthma.

Localization and quantification of regional and segmental air trapping in asthma.

OBJECTIVE: To assess the feasibility of volumetric and densitometric software to localize and quantify signs of regional air trapping after methacholine bronchoprovocations in asthma. METHODS: Eight atopic subjects with mild-to-moderate asthma using short-acting beta2-agonists only, with hyperresponsiveness to methacholine, were evaluated. Low-dose baseline expiratory 16-slice multidetector computed tomography scans before and after a methacholine bronchoprovocation were acquired. MeVisPULMO3D software (Bremen, Germany) was applied to the scans, providing quantitative information on volume and density measures of the total lung and each lobe. RESULTS: After methacholine, the expiratory scan showed a median (interquartile range) increase in volume of 534 mL (357-1279 mL), a decrease in lung density (mean and 15th percentile) of 52 Hounsfield Units (HU) (116-39 HU) and 34 HU (78-25 HU), respectively, and an increase in percentage low attenuation areas of 3% (2%-6%) for the total lung, with similar patterns in individual lung lobes. The right and left lower lung lobes showed the largest increases in air trapping, 211 mL (117-363 mL) and 229 mL (155-315 mL), respectively, versus a volume increase of 70 mL (20-249 mL), 26 mL (-16-92 mL), and 91 mL (-28-241 mL) for the right upper, middle, and left upper lobes, respectively. Volume changes in the lower lobes were associated with baseline forced expiratory flow between 25% and 75% of forced vital capacity, whereas low attenuation areas changes in the lower lobes were not. CONCLUSIONS: This study suggests that multidetector computed tomography scans are able to localize and quantify regional air trapping in asthma after methacholine bronchoprovocations. Volumetric measurements of the lobes as compared to densitometric measurements are superior in detecting local air trapping in gravity-dependent areas of the lung.

FVC to slow inspiratory vital capacity ratio: a potential marker for small airways obstruction.

BACKGROUND: The ratio of FVC to slow inspiratory vital capacity (SVC) has been reported to reflect small airways obstruction, but its validity as such is still unclear. The aim of this study was to assess the applicability of the FVC/SVC ratio as a marker of small airways function in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX), which is a disorder in which predominantly small airways obstruction causes progressive airflow limitation. METHODS: The FVC/SVC ratio was analyzed both cross-sectionally and longitudinally in 39 patients (26 men) with BOS after bilateral LTX (median age, 47 years; interquartile range [IQR], 35 to 54 years), and 36 bilateral lung transplant recipients without BOS (14 men; median age, 46 years; IQR, 41 to 53 years). RESULTS: The FVC/SVC ratio decreased significantly during follow-up in patients with BOS stages 1 and 2, by 2.2% and 4.4%, respectively, from baseline (p < 0.001). This decrease was not significantly associated with the decrease in FEV(1). The FVC/SVC ratio increased, though not significantly, in the group in which BOS did not develop by 1.1%, which is a significant difference from the average fall of 4.4% in the group in which BOS developed. CONCLUSIONS: Significant, yet small decreases in FVC/SVC ratio occur in patients in whom BOS develops, independent from changes in FEV(1). At a group level, FVC/SVC ratio is able to detect small airways changes. These results merit prospective studies to determine the sensitivity of FVC/SVC ratio to quantifying small airways dysfunction at an individual level and in other airway diseases.

Technical description of endoscopic ultrasonography with fine-needle aspiration for the staging of lung cancer.

BACKGROUND: Endoscopic ultrasonography (EUS) is a novel method for staging of the mediastinum in lung cancer patients. The recent development of linear scanners enables safe and accurate fine-needle aspiration (FNA) of mediastinal and upper abdominal structures under real-time ultrasound guidance. However, various methods and equipment for mediastinal EUS-FNA are being used throughout the world, and a detailed description of the procedures is lacking. A thorough description of linear EUS-FNA is needed. METHODS: A step-by-step description of the linear EUS-FNA procedure as performed in our hospital will be provided. Ultrasonographic landmarks will be shown on images. The procedure will be related to published literature, with a systematic literature search. RESULTS: EUS-FNA is an outpatient procedure under conscious sedation. The typical linear EUS-FNA procedure starts with examination of the retroperitoneal area. After this, systematic scanning of the mediastinum is performed at intervals of 1-2cm. Abnormalities are noted, and FNA of the abnormalities can be performed. Specimens are assessed for cellularity on-site. The entire procedure takes 45-60 min. CONCLUSIONS: EUS-FNA is minimally invasive, accurate, and fast. Anatomical areas can be reached that are inaccessible for cervical mediastinoscopy. EUS-FNA is useful for the staging of lung cancer or the assessment and diagnosis of abnormalities in the posterior mediastinum.

Initial improvements in lung function and bronchial hyperresponsiveness are maintained during 5 years of treatment with inhaled beclomethasone dipropionate and terbutaline.

OBJECTIVES: Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d. METHODS: Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period. RESULTS: After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP. CONCLUSIONS: We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.