Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

Computed tomography diagnosis of tracheobronchopathia osteochondroplastica.

Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease characterized by the presence of osseous and cartilaginous submucosal nodules projecting into the tracheobronchial tree. Most cases are asymptomatic and discovered incidentally at post-mortem. We identified a case of TO on thoracic spiral CT and confirmed the diagnosis of bronchoscopy. This article reviews the imaging characteristics of TO, and shows the 3-D virtual bronchoscopic and multiplanar reconstruction appearances of TO.

Implementation of a split-night protocol to improve efficiency in assessment and treatment of obstructive sleep apnoea.

In Australia, unmet demand for sleep study services is resulting in protracted waiting lists and treatment delays for those in need. This present study gauged efficiency gains that could be achieved by implementing a split-night protocol within the laboratory. Results demonstrate improved technical efficiency by at least 15%, reducing time to treatment for the most severe cases and increasing patient throughput within the clinic. With over 56,000 sleep studies carried out annually, this technique has significant utility in evidence-based practice.

Impact on readmission rates and mortality of a chronic obstructive pulmonary disease inpatient management guideline.

AIMS: Chronic obstructive pulmonary disease (COPD) is a common condition associated with considerable morbidity, mortality and hospital admissions. However, published COPD management guidelines have major limitations and lack practical summaries. We aimed to optimally develop, implement, and evaluate a multidisciplinary COPD inpatient management 'ACCORD' guideline, including prompts for comprehensive day one assessments through to a discharge criteria checklist. METHOD: Two intervention and two control public teaching hospitals in Adelaide, South Australia, took part, with pre-intervention (721 COPD admissions over 7 months) and intervention phases (509 COPD admissions over 7 months). During the intervention stage the ACCORD guideline was placed in the case notes on the day of admission or soon after. Readmissions were categorized as either emergency or elective and compared between the study arms, as were mortality and potential confounders (age, gender, number of comorbidities), with Poisson regression analysis. RESULTS: Of case notes of eligible COPD patients, 60% had the ACCORD guideline placed, of which 76% had evidence of use as judged by completion of guideline entry and tick boxes. The ACCORD guideline was associated with an increase in elective admissions and a reduction in emergency admissions in the intervention group in relation to the control group (P < 0.01), with no difference in overall admissions or death rates. CONCLUSIONS: The ACCORD guideline was associated with a shift from emergency admissions to more planned elective care, suggesting more proactive care of health problems, but without overall reduction in admissions.

Single-cell analysis: a novel approach to tumour necrosis factor-alpha synthesis and secretion in sarcoidosis.

Tumour necrosis factor (TNF)-alpha is thought to be a key early cytokine in the pathogenesis of sarcoidosis, despite conflicting data. Largely the product of mononuclear phagocyte activation, it is unclear whether TNF-alpha production at disease sites is a feature of all mononuclear phagocytes that accumulate there or whether it is secreted by a subset of these cells. Using the reverse haemolytic plaque assay, the aims of this study were to determine if the upregulation of TNF-alpha could be confirmed and to investigate whether this was monocyte or macrophage specific. The reverse haemolytic plaque assay allows the measurement of cytokine production at a single cell level. A greater number of alveolar macrophages produced TNF-alpha compared to autologous monocytes in sarcoidosis but not in controls and, based on cell size, it was confirmed that this was the product of more mature macrophages and that the secretion of TNF-alpha by monocytes and macrophages was heterogeneous: not all monocytes and macrophages secrete TNF-alpha. No differences in the average levels of TNF-alpha secretion by peripheral blood monocytes or alveolar macrophages were observed. This study has demonstrated that a subset of mononuclear phagocytes, mature macrophages, are responsible for tumour necrosis factor secretion and this could have implications for targeted management in sarcoidosis in the future.

Tumour necrosis factor-alpha production in fibrosing alveolitis is macrophage subset specific.

BACKGROUND: Previous studies have revealed that tumour necrosis factor (TNF)-alpha is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-alpha secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. In particular, we wished to assess whether TNF-alpha levels differ between SSc patients with FA (FASSc) and a nonfibrotic group. METHODS: The reverse haemolytic plaque assay was used to evaluate the secretion of cytokine at a single cell level while immunostaining allowed subtyping of AMs and Mos. RESULTS: This study demonstrated a difference in total TNF-alpha levels produced by AMs when the levels in subjects with FA (cryptogenic FA and FASSc) were compared to levels in either SSc patients without FA (P = 0.0002) or normal healthy controls (P < 0.001). In addition, AMs from patients with FASSc secreted more TNF-alpha than those of patients with no FA (P = 0.003). In contrast, there were no significant differences in Mo TNF-alpha secretion between the groups. A positive correlation was found between total TNF-alpha level and number of neutrophils obtained by bronchoalveolar lavage from patients with FA (r = 0.49, P < 0.04). Finally, it was demonstrated that there was significant heterogeneity of TNF-alpha secretion and that a numerically significant subset of mononuclear phagocytes, RFD7, was responsible for more than 80% of TNF-alpha production. CONCLUSION: By demonstrating the primary cell source of TNF-alpha in FASSc, more accurately targeted, possibly localized, anti-TNF strategies might be employed with success in the future.

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and deterioration in health. It is associated with significant morbidity, mortality and costs to health care systems. Care strategies, such as outreach nursing in the community, may reduce this burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTS were contacted for other published and unpublished studies. SELECTION CRITERIA: Only randomised control trials of patients with COPD were included. The intervention was an outreach nurse visiting patients in their homes, providing support, education, monitoring patient status and providing liaison with physicians. Interventions that used nurse practitioners who provided therapeutic intervention were also included. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. MAIN RESULTS: Four studies were found. Three assessed mortality following twelve months of care (n=96, 152 and 301), and one after seven months(n=75). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio 0.72; 95 % confidence interval 0.43, 1.21. Post hoc subgroup analysis suggested that mortality was reduced by the outreach nursing programme in patients with less severe disease. Significant improvements in health related quality of life were reported in one study in moderate COPD, but not in a study in patients with severe disease. No changes in lung function or exercise performance were found in the studies where data were available. Hospital admissions were reported in only one study in patients with severe disease and no benefit was observed. A further search was conducted in July 2000 did not yield any more studies for inclusion. REVIEWER'S CONCLUSIONS: Patients with moderate COPD may have mortality and health related quality of life gains from a nursing outreach programme, but there are no data about reductions in hospital utilisation. Patients with severe COPD do not appear to have benefit from such programmes and one large study found no reduction in hospital admissions in such patients.

Increased effective lung volume following lung volume reduction surgery in emphysema.

STUDY OBJECTIVES: Lung volume reduction surgery (LVRS) for emphysema has a variable effect on spirometry with improvement linked to increases in lung elastic recoil. The mechanism by which recoil increases following LVRS has not been described completely. This study examines preoperative and postoperative pulmonary function to describe a mechanism for changes in airflow obstruction. DESIGN: Change in pulmonary function following LVRS. Setting : Public teaching hospital in Australia. PATIENTS: Patients with severe emphysema and pulmonary function measurements made before and after LVRS. MEASUREMENTS: Routine pulmonary function testing performed with ventilated lung alveolar volume (VA) derived from the gas transfer measurement used as a proxy for the effective lung volume. RESULTS: Pulmonary function tests from 36 consecutive patients with measurements made at the same laboratory were analyzed. The mean FEV(1) was 29.1% predicted presurgery and increased following LVRS from 0.900 L (SD, 0.427 L) to 1.283 L (SD, 0.511 L; p < 0.0001) and TLC (143% predicted) decreased from 8.19 L (SD, 1.492 L) to 7.07 L (SD, 1.52 L; p < 0.0001; n = 35). The mean VA increased by 0.674 L (SD, 0.733 L) from 4.04 to 4.72 L (p < 0.0001; n = 34). The change in FEV(1) correlated well with the change in VA (r = 0.63). The change in FEV(1) in those patients whose VAs did not increase (n = 7) was not significant. CONCLUSIONS: The increase in VA reflects an increase of functional or ventilating lung volume and is associated with an improvement in spirometry following LVRS.

Prevalence, morbidity and management of adult asthma in South Australia.

This paper reviews asthma-related data obtained between 1987 and 1997 from self-report population surveys of adults in South Australia. A multistage, systematic, clustered area sample of adults (>15 years) was selected from a random sample of Australian Bureau of Statistics collector districts, and interviewed at home by trained health interviewers. The self-report prevalence of doctor-diagnosed asthma increased from 5.6% in 1987 to 12.2% in 1997. Morbidity measured as days lost from usual activities and nights awakened by asthma remained high, but hospitalization rates are trending down. The ownership of asthma action plans peaked in 1995 and has declined. The ownership of peak flow meters increased between 1992 and 1997, and the ownership of nebulisers remained constant. Evidence-based interventions are required to improve asthma management.

Videoscopic lung volume reduction surgery in an Australian public teaching hospital.

BACKGROUND: Lung volume reduction surgery (LVRS) has been a frequent literature topic in emphysema management recently. Opinions differ in regard to usefulness, efficacy, and selection criteria. AIMS: To present the results of our first 55 bilateral videoscopically resected group, with follow-up of up to three years, and to present some of the local methodology problems faced. METHODS: Thirty-nine men and 16 women, age range 40-77, had either upper lobe (42), mixed (two), or lower lobe (11) resections without buttressing (except for unilateral buttressing in several of the latter patients as part of an intrapatient comparison trial) according to their pattern of emphysema determined by CT and perfusion scanning. RESULTS: Thirty day mortality was 5.5%. Follow-up pulmonary function is available for 44 patients, and demonstrates a mean 51% improvement in FEV1, and significant improvement in FVC, PaO2, dyspnoea indices and walking distance, with a reduction in mean RV, TLC, PaCO2. FEV1 improvement is maintained above baseline at three years. Lower lobe surgery outcomes are at least as good as their upper lobe counterparts. CONCLUSIONS: Outcomes confirm improvements reported elsewhere, and suggest that videoscopic resection may provide worthwhile benefit to lower lobe patterns of emphysema. Other managment issues are discussed.

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and deterioration in health. It is associated with significant morbidity, mortality and costs to health care systems. Care strategies, such as outreach nursing in the community, may reduce this burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for patients with COPD in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and hospital service utilisation. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTS were contacted for other published and unpublished studies. SELECTION CRITERIA: Only randomised control trials of patients with COPD were included. The intervention was an outreach nurse visiting patients in their homes, providing support, education, monitoring patient status and providing liaison with physicians. Interventions that used nurse practitioners who provided therapeutic intervention were also included. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. MAIN RESULTS: Four studies were found. Three assessed mortality following twelve months of care (n=96, 152 and 301), and one after seven months(n=75). Meta-analysis demonstrated that mortality was not significantly reduced by the intervention, Peto Odds Ratio 0.72; 95 % confidence interval 0.43, 1.21. Post hoc subgroup analysis suggested that mortality was reduced by the outreach nursing programme in patients with less severe disease. Significant improvements in health related quality of life were reported in one study in moderate COPD, but not in a study in patients with severe disease. No changes in lung function or exercise performance were found in the studies where data were available. Hospital admissions were reported in only one study in patients with severe disease and no benefit was observed. REVIEWER'S CONCLUSIONS: Patients with moderate COPD may have mortality and health related quality of life gains from a nursing outreach programme, but there are no data about reductions in hospital utilisation. Patients with severe COPD do not appear to have benefit from such programmes and one large study found no reduction in hospital admissions in such patients.

Multiple respiratory symptoms predict quality of life in chronic lung disease: a population-based study of Australian adults.

STUDY OBJECTIVES: Previous studies have shown that it is possible to improve the health-related quality of life (HRQoL) of chronic lung disease (CLD) patients without a concurrent change in morbidity. A valid CLD index that discriminates between different levels of CLD severity and is associated with HRQoL status is an important tool for primary care settings. In this study a symptom-based CLD index was assessed for its validity and relationship with HRQoL in a representative Australian population sample. The study also measured the prevalence of self-reported CLD. DESIGN: Representative population survey of adults aged 18 years and over using a multistage, systematic, clustered area sample. SETTING: Metropolitan Adelaide and country centres in South Australia with a population of over 1000 persons. PARTICIPANTS: Three hundred twenty-nine adults with CLD identified through a representative population survey of 3010 South Australians. MEASUREMENTS AND RESULTS: The CLD index and the SF-36 were administered to participants to assess the association between each subscale of the CLD index with each HRQoL scale. The CLD index was also used to assess the prevalence of CLD and the distribution of severity in self-reported CLD in the South Australian population. Each symptom sub-scale of the CLD index was significantly correlated with all scales of the SF-36. The prevalence of CLD as measured by the CLD index was 7.7% (mild), 2.2% (moderate) and 1.0% (severe). CONCLUSIONS: In the Australian context the CLD index is a reliable patient interview instrument that can be used to assess the effects of CLD on general HRQoL, improve assessment, and lead to interventions for physicians and their patients.

A South Australian population survey of the ownership of asthma action plans.

OBJECTIVE: To examine the relationships between ownership of written asthma action plans, asthma morbidity, use of devices, and patients' perceptions of their asthma management. DESIGN AND SETTING: A random population survey (in 1996) of the South Australian population aged 15 years or over, using interviewers to administer a questionnaire. PARTICIPANTS: People who reported that they had current, doctor-diagnosed asthma. MAIN OUTCOME MEASURES: Prevalence of written asthma action plans; night-time awakenings from asthma; ownership of peak flow meters; and people's perceptions of their asthma management. RESULTS: The ownership of asthma action plans by people with self-reported asthma was 33% and has declined since 1995 (42%; P < 0.001). Fifteen per cent were awakened weekly or more frequently by asthma symptoms. These people were more likely to have a peak flow meter and a written action plan, but less likely to consider they had been provided with enough information about their asthma, to feel comfortable managing their asthma, or to find it easy to see their doctor. Having a written asthma action plan was associated with regular corticosteroid use, understanding asthma, having enough information and owning a peak flow meter. CONCLUSIONS: Ownership of asthma action plans in South Australia is suboptimal. Before we develop new strategies to improve asthma outcomes, we must determine whether there is a need to target people with less severe asthma and/or improve the use of guidelines by health professionals.

Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.

Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids.

T-cell receptor gene usage in patients with fibrosing alveolitis and control subjects.

BACKGROUND: Fibrosing alveolitis is characterized by inflammation, fibrosis and increased numbers of activated CD4+ T-cells in the lower respiratory tract. The aims of this study were to compare the T-cell antigen receptor repertoire in the lungs of subjects with fibrosing alveolitis systemic sclerosis (FASSc) with cryptogenic fibrosing alveolitis (CFA) and normal control subjects, to determine whether FASSc is driven by a specific T-cell trigger and is determined by a T-cell driven immune response, and to assess the clonality of CD4+ and CD8+ TcR usage in subjects with FASSc. MATERIALS AND METHODS: We used reverse transcription polymerase chain reaction with specific V alpha- and V beta-chain primers to identify the TcR gene usage in biopsy material, bronchoalveolar lavage fluid or peripheral blood from our subjects. RESULTS: We found individual-specific restriction of V alpha- and V beta-chain usage in lung biopsies from patients and control subjects. To establish whether this was due to expression bias in the CD4+ or CD8+ T-cells and was restricted to the lung, the alpha beta-T-cell receptor chain usage was assessed in T-cell subsets separated from the lungs of patients with fibrosing alveolitis and was compared with that of the peripheral blood. There was no consistent difference in the expression of any variable family chain among the population studied, although there was a significant difference between lung and peripheral blood lymphocyte V beta-families in CD8+ T-cells (P = 0.0007). CONCLUSION: We conclude that there is individual TcR V alpha- and V beta-expression bias in subjects with fibrosing alveolitis.

The effect of a respiratory home nurse intervention in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmomary disease (COPD) is associated with substantial mortality, morbidity, and costs to the health care system. With the increasing interest in outreach care programmes it is important to evaluate their impact upon patients and health services, for conditions such as COPD. AIM: To determine the effectiveness of an outreach respiratory nurse in a shared care approach, with collaboration between general practitioners and hospital services, in the management of patients with severe COPD. METHODS: Patients with severe COPD attending The Queen Elizabeth Hospital, Adelaide participated in a randomised controlled trial of a home based nursing intervention (HBNI) over 12 months with outcome measures including mortality rate, hospital service utilisation, FEV1 and health related quality of life (HRQL) using a modified Dartmouth Primary Care Co-operative Quality of Life questionnaire. RESULTS: There were 48 subjects in each study arm, with no differences in mortality rate (eight deaths in the HBNI group and seven in the control group), hospital admissions, length of stay, number of outpatient and Emergency Service visits. The study had inadequate follow-up of FEV1 and HRQL within the control group. Within the HBNI group, a small improvement in HRQL (in three of ten indices measured) was demonstrated, despite a deterioration in FEV1 (11% reduction, p=0.04) compared to baseline. Quality of life of HBNI subjects' carers did not change. CONCLUSION: An increased level of care given by an outreach respiratory nurse in a shared care approach for patients with severe COPD produced small improvements in HRQL but did not result in the prevention of deaths or reduced health care utilisation.

Adhesion molecule expression in the lung: a comparison between normal and diffuse interstitial lung disease.

Cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues. In chronic inflammatory diseases, upregulation of the expression of these molecules may contribute to the persistent inflammatory process. The aim of this study was to determine whether there is evidence of adhesion molecule expression in chronically inflamed lung. Soluble adhesion molecules in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunoassay in 54 patients with chronic interstitial lung diseases and 16 normal controls. Adhesion molecule expression in fibrosing alveolitis (FA) lung and in control lung was assessed using immunohistology and reverse transcription-polymerase chain reaction (RT-PCR) amplification. Soluble intercellular adhesion molecule-1 (ICAM-1) was detected in all but two subjects. There was no difference in ICAM-1 concentration between disease groups and normal subjects. In contrast, soluble E-selectin was detected in 17 of the 70 subjects and was significantly associated with the presence of lung disease (p=0.0173). Furthermore, the presence of soluble E-selectin was associated with a raised lymphocyte percentage in BALF (p=0.0069). Soluble VCAM was only detected in five of the 70 subjects (two normals, three patients). There was no difference in adhesion molecule expression in lung parenchyma between FA and controls assessed by immunohistology and RT-PCR. The most striking finding of our study was the universal expression of intercellular adhesion molecule-1 in both normal and diseased lung, emphasizing the important role of the lung in immune function. Upregulation of E-selectin may contribute to inflammatory cell accumulation in chronic interstitial lung diseases.

Chlorofluorocarbon-free inhalation devices in asthma: are there clinical implications?

Alternative non-chlorofluorocarbon (CFC) propellants have been developed and have been shown to be safe alternatives to CFC propellants. Salbutamol (albuterol) and beclomethasone dipropionate (BDP) in metered dose inhalers (MDIs) have been most studied. Salbutamol sulfate non-CFC MDIs have remained as a suspension formulation, and there is good evidence that salbutamol sulfate non-CFC MDIs are equivalent to salbutamol sulfate CFC MDIs. BDP non-CFC MDIs have a new formulation which is a solution and has a significantly smaller particle size than BDP delivered from CFC MDIs. This has resulted in more of the metered dose from the non-CFC MDI reaching the lower respiratory tract, with a consequent reduction of the dose deposited in the throat. This change allows a smaller dose of the non-CFC BDP to be equivalent to the CFC formulation. However, efficacy studies will be needed with other medications that are delivered in non-CFC MDIs because this finding with BDP relates to the solution formulation and particle size. The non-CFC propellant hydrofluoroalkane (HFA)-134a functions better at a lower temperature than its CFC comparator.

The source and role of RANTES in interstitial lung disease.

The chemokine "regulated on activation, normal T-cell expressed and secreted" (RANTES) is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T-cells and eosinophils. These cells accumulate in the lungs of patients with sarcoidosis and fibrosing alveolitis. The purpose of this study was to determine whether RANTES mediates the inflammatory cell influx in these diffuse lung diseases. Cell types and number of bronchoalveolar cells expressing RANTES protein were investigated by immunocytochemistry using lavage cells obtained from 22 patients and 11 control subjects. Subsequently, RANTES messenger ribonucleic acid (mRNA) was semiquantitated using reverse transcription polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets in 26 patients and 13 control subjects. Cells expressing RANTES mRNA were identified by in situ hybridization. RANTES protein expression in lower respiratory tract (LRT) cells was identified in all study groups. The percentage of RANTES+ lavage cells in sarcoidosis was higher than in controls. RANTES was localized in the cytoplasm, mainly in alveolar macrophages (CD68+ cells) in sarcoidosis, and both in alveolar macrophages and eosinophils in fibrosing alveolitis. The same cell types which expressed RANTES protein expressed RANTES mRNA, as assessed by in situ hybridization. Sarcoidosis patients had higher levels of RANTES mRNA than the other groups. RANTES protein was higher in individuals with abnormal lymphocyte numbers: RANTES protein and mRNA expression was significantly correlated with lavage CD45RO+ lymphocyte numbers. These results indicate that RANTES may mediate T-lymphocyte influx in diffuse lung disease, particularly sarcoidosis. Moreover, they suggest that the cellular source of RANTES is the alveolar macrophage in sarcoidosis, and both macrophages and eosinophils in fibrosing alveolitis.