Switching to the Dry-Powder Inhaler Easyhaler®: A Narrative Review of the Evidence.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler® device, a high- or medium-high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. Enhanced feature (slides, video, animation) (MP4 43768 kb).

Preference for Easyhaler® Over Previous Dry Powder Inhalers in Asthma Patients: Results of the DPI PREFER Observational Study.

OBJECTIVE: To study patient preference for and satisfaction with the Easyhaler® device and to assess ease of training and use of the inhaler in patients previously treated with a variety of dry powder inhalers (DPIs). METHODS: We designed a non-interventional, cross-sectional, single-visit observational study of adult patients with persistent asthma referred to specialized care who had previously been treated with DPI inhalers for at least 3 months. Once clinical baseline data had been checked, patients filled in questionnaires on asthma control (GINA 2019), Feeling of Satisfaction with the Inhaler (FSI-10), and adherence (TAI and Morisky-Green questionnaires). Thereafter, all patients were trained in the use of Easyhaler. We assessed ease of use and satisfaction (FSI-10) with Easyhaler, as well as inhaler device preferences. RESULTS: We recruited 502 patients (mean age, 50.2 ± 16.2 y; 63.1% female), of whom 485 were evaluable. In response to the main objective of the study, we compared the values of the self-completed adapted FSI-10, to measure satisfaction with the inhaler. A significantly higher score in each item of the questionnaire was recorded for Easyhaler. Overall, 38% of patients showed exclusive preference for Easyhaler (compared with 15% for the previous device) or were evenly matched in 46% of cases. CONCLUSION: In the present study, Easyhaler achieved better patient ratings in terms of preference and satisfaction than previously used DPI devices. In order to improve asthma adherence strategies, patient preferences and device choice should be taken into account.

Prevalence of modifiable factors limiting treatment efficacy of poorly controlled asthma patients: EFIMERA observational study.

Several modifiable factors leading to poor asthma control have been described. We aimed to determine the proportion of patients with inadequate treatment, adherence to it, or critical mistakes with inhaler technique, and their impact on asthma control. We conducted a cross-sectional multicenter observational study including asthma patients referred from primary to specialist care for the first time. Data collected were adequate prescription according to guidelines, treatment adherence, and disease control. Of the 1682 patients (age 45 ± 17 years, 64.6% men), 35.9% showed inadequate prescription, 76.8% low adherence, and 17% critical mistakes with inhaler technique, with significantly less critical mistakes among Easyhaler users versus other dry powder inhaler users (10.3 versus 18.4%; p < 0.05). Factors related to bad asthma control were inadequate prescription (OR: 3.65), non-adherence to treatment (OR: 1.8), and inhaler misuse (OR: 3.03). A higher number of risk factors were associated with a higher probability of having badly controlled asthma.

Correction to: A Multicenter, Observational, Prospective Study of the Effectiveness of Switching from Budesonide/Formoterol Turbuhaler® to Budesonide/Formoterol Easyhaler®.

Unfortunately, the mean difference in change from baseline ACT was incorrectly reported in the abstract as 19.0 vs. 20.8 instead of 18.9 vs. 20.7.

A Multicenter, Observational, Prospective Study of the Effectiveness of Switching from Budesonide/Formoterol Turbuhaler® to Budesonide/Formoterol Easyhaler®.

INTRODUCTION: In real-life practice, asthma remains poorly controlled, with a considerable burden on patients' quality of life. Budesonide/formoterol (B/F) Easyhaler® has demonstrated similar dose consistency, therapeutic equivalence, and equivalent bronchodilator efficacy to B/F Turbuhaler®, but no real-life comparisons are yet available in patients switching from B/F Turbuhaler® to B/F Easyhaler®. METHODS: The primary objective of this real-life, non-interventional, observational study was to show non-inferiority of asthma control when adult patients in Swedish primary care with persistent asthma switched from B/F Turbuhaler® to B/F Easyhaler®. At visit 1, baseline demographic and endpoint data were recorded, and eligible patients switched to B/F Easyhaler®. The study comprised a control visit (visit 2) and a concluding examination (visit 3) after 12 weeks. Asthma control was assessed using the Asthma Control Test (ACT). The mini-Asthma Quality of Life Questionnaire (AQLQ) and lung function test were performed, and participants and investigators answered questionnaires about ease-of-use and teaching. RESULTS: A total of 117 patients were enrolled in the on-treatment population; 81 (64.8%) were female. At visit 3, B/F Easyhaler® demonstrated non-inferiority to B/F Turbuhaler®; the mean difference in change from baseline ACT was statistically significant (18.9 vs. 20.7, respectively; p < 0.0001) and met the non-inferiority criteria of B/F Easyhaler® being greater than - 1.5 points versus the reference product. Asthma was well controlled in 62 (53.0%) patients at baseline, increasing to 83 patients (70.9%) at visit 3. Patients experienced statistically significant improvements in mini-AQLQ score after B/F Easyhaler® treatment and lung function remained stable across the treatment period. B/F Easyhaler® was easy to learn and prepare for use. CONCLUSION: This real-life, non-interventional, non-inferiority study in adults with persist asthma demonstrates equivalent or better disease control when patients switch from B/F Turbuhaler® to B/F Easyhaler®. A further study with direct comparison between treatments could add to the understanding of inhaler switch. FUNDING: Orion Corporation, Orion Pharma.

Asthma patient satisfaction with different dry powder inhalers.

BACKGROUND: The preferences and opinions of patients are important when choosing the optimal inhaler device for asthma management. We compared patient satisfaction of three dry powder inhalers in patients with moderate to severe asthma. METHODS: We selected a group of patients treated with EasyhalerTM (n = 164) and a second group of patients treated with TurbuhalerTM (n = 100) or DiskusTM (AccuhalerTM) (n = 64) from the register of an observational, multicenter study. Data of patients were paired according to age, gender, and asthma severity. Patient satisfaction with the inhaler type was assessed with the specific 'Feeling of Satisfaction with Inhaler' (FSI-10) questionnaire. RESULTS: Specific satisfaction with inhaler was statistically significantly higher with EasyhalerTM, as well as the percentage of patients with high satisfaction with inhaler. (FSI-10 score ≥43). Scores for EasyhalerTM were also statistically significantly better for individual FSI-10 items such as learning how to use, inhaler preparation, inhaler use, weight and size, and portability. There were no significant differences in asthma control (ACT, Mini-AQLQ) and adherence (TAI global score). CONCLUSIONS: Specific satisfaction with inhaler was higher with EasyhalerTM in a homogeneous population of patients with moderate to severe asthma. However, the relationship between satisfaction with the inhaler and adherence and asthma control deserves more investigation.

Impact of patient satisfaction with his or her inhaler on adherence and asthma control.

Background: Asthma guidelines recommend considering patient preferences for inhaler choice. However, few studies have assessed the impact of patient satisfaction with an inhaler on adherence and health outcomes. Objective: To assess the impact of patient satisfaction with an inhaler on adherence and health outcomes in asthma. Methods: In a cross-sectional, observational, multicenter study, 778 patients with moderate or severe asthma and who were treated with maintenance inhalers completed a number of scales and questionnaires: the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the Treatment Satisfaction Questionnaire for Medication, the Test of Adherence to Inhalers (TAI), the Morisky-Green questionnaire, and the Asthma Control Test (ACT). Results: The study population was categorized according to a median FSI-10 score as high (49.4%) and low (50.6%) satisfaction with their inhaler. Logistic regression analysis showed that high specific satisfaction with an inhaler was associated with the younger age group (odds ratio [OR] 0.976 [95% confidence interval {CI} 0.965-0.987]); male gender (OR 1.725 [95% CI 1.187-2.507]); controlled asthma: ACT score ≥ 20 (OR 1.664 [95% CI 1.133-2.445]); high general satisfaction with treatment (OR 4.861 [95% CI 3.335-7.085]); high adherence to inhaler: TAI score ≥ 46 (OR 1.546 [95% CI 1.025-2.332]); nonsevere asthma (OR 1.056 [95% CI 0.648-1.721]); and no trouble with inhaler use (OR 0.401 [95% CI 0.174-0.922]). Conclusion: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.

Dose uniformity of budesonide Easyhaler® under simulated real-life conditions and with low inspiration flow rates.

Budesonide Easyhaler® multidose dry powder inhaler is approved for the treatment of asthma. Objectives were to determine the delivered dose (DD) uniformity of budesonide Easyhaler® in simulated real-world conditions and with different inspiration flow rates (IFRs). Three dose delivery studies were performed using 100, 200, and 400 µg/dose strengths of budesonide. Dose uniformity was assessed during in-use periods of 4-6 months after exposure to high temperature (30°C) and humidity (60% relative humidity) and after dropping and vibration testing. The influence of various IFRs (31, 43, and 54 L/min) on the DD was also investigated. Acceptable dose uniformity was declared when mean DD were within 80-120% of expected dose; all data reported descriptively. DD was constant (range: 93-109% of expected dose) at all in-use periods and after exposure to high temperature and humidity for a duration of up to 6 months. DD post-dropping and -vibration were unaffected (range 98-105% of expected dose). Similarly, DD was constant and within 10% of expected dose across all IFRs. Results indicate that budesonide Easyhaler® delivers consistently accurate doses in various real-life conditions. Budesonide Easyhaler® can be expected to consistently deliver a uniform dose and improve asthma control regardless of high temperature and humidity or varying IFR.

Usage and usability of one dry powder inhaler compared to other inhalers at therapy start: an open, non-interventional observational study in Poland and Germany.

INTRODUCTION: Inhalation is the preferred route of drug administration for patients with asthma or COPD. It is generally predicted that there is a high error rate in inhaler usage, especially at the therapy start. The primary objective of this study was the validation of a questionnaire that can be used for assessing a successful inhalation technique, patient satisfaction as well as the compliance in daily practice.The secondary objective was to examine the "real-life" usage of one inhalation device in comparison with other devices at the start of the therapy. MATERIAL AND METHODS: This open, multi centre and non-interventional study was designed to examine usage and usability of dry powder inhaler Easyhaler® (EH) (Orion Pharma, Finland) and other inhalers assessed by the physicians as well as by the patients. Inclusion criteria for patients were a physician-diagnosis of COPD or asthma or children with asthmatic disease, therapy start with an inhalation device and no or only few experiences with inhaler usage (inhaler usage for not more than 3 months). Each physician enrolled an equal number of patients in each group. RESULTS: 263 adult/adolescent patients with asthma and 115 with COPD as well as 164 children with asthmatic disease were enrolled. 49.4% of the adult/adolescent patients with asthma used an EH and 50.6% other inhalers. In the case of COPD, 47.8% were treated with an EH and 52.2% used other inhalation devices. Finally, 50.6% of the children with asthmatic disease used an EH and 49.4% were treated with other inhalers. Inhaler usage, patient satisfaction, compliance and patients assessments of usability were better when the patients used an EH. Inconvenient features were mainly documented for other inhalers. The analysis of Cronbachs alpha clearly showed the consistency of the received data from all patients. In addition, there was a large association between the assessment of the inhaler usage and the general assessment of the used inhaler in all patient groups. CONCLUSION: The results of this study show that investigators found EH easy to teach, the patients found it easy to use and their satisfaction with the device was high in comparison to other inhalation devices. Thus EH can be matched to many patients already at the therapy start. In addition, the high consistency of the received data and large association of the assessment of the inhaler usage and the general assessment of the inhaler indicate that the used questionnaires were appropriate tools to examine usage and usability of inhaler devices in adult patients and children.

Inspiratory flows through dry powder inhaler in chronic obstructive pulmonary disease: age and gender rather than severity matters.

BACKGROUND: Dry powder inhalers (DPIs) are inspiratory flow driven and hence flow dependent. Most patients with chronic obstructive pulmonary disease (COPD) are elderly and have poor lung function. The factors affecting their inspiratory flows through inhalers are unclear. OBJECTIVE: To study peak inspiratory flows (PIFs) and their determinants through a DPI in COPD patients of varying age and severity. METHODS: Flow-volume spirometry was performed in 93 COPD patients. Maximum PIF rates were recorded through an empty Easyhaler (PIF(EH); Orion Corporation, Espoo, Finland), a DPI that provides consistent dose delivery at inhalation rates through the inhaler of 28 L/min or higher. RESULTS: The mean PIF(EH) was 54 L/min (range 26-95 L/min) with a coefficient of variation of 7%. All but two patients were able to generate a flow of > or = 28 L/min. In a general linear model, the independent determinants for PIF(EH) were age (P = 0.02) and gender (P = 0.01), and forced expiratory volume in 1 s (FEV(1)) expressed as percent predicted was not a significant factor. The regression model accounted only for 18% of the variation in PIF(EH). CONCLUSION: In patients with COPD, age and gender are more important determinants of inspiratory flow through DPIs than the degree of expiratory airway obstruction. Most COPD patients with varying age and severity are able to generate inspiratory flows through the test inhaler that is sufficient for optimal drug delivery to the lower airways.

Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study.

BACKGROUND: Smoking cessation is the best possible way to prevent the progression of smoking related airway diseases. However, the effect and time scale of smoking cessation on airway inflammation/remodelling are largely unknown. This prospective study evaluated the effects of smoking cessation on induced sputum (IS) neutrophils, matrix metalloproteinases (MMP-7, -8, -9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). METHODS: A total of 61 subjects participated in the study; 17 stopped smoking for 3 months and 9 for 6 months. The proportion of IS neutrophils and the levels of MMPs and TIMP-1 by ELISA were determined at baseline and at 3 and 6 months after cessation. RESULTS: In the smokers, baseline IS neutrophils, MMPs and TIMP-1 were significantly higher compared to non-smokers. Levels of MMP-7, -8 and TIMP-1 decreased nearly to those of non-smokers but the levels of MMP-9 increased significantly from the baseline of the same subjects at 3 months after cessation (p = 0.009) with no significant decline at 6 months after cessation. CONCLUSIONS: Sputum MMP-9 remained elevated after 6 months of smoking cessation, which may contribute to ongoing lung damage typical of COPD.

Thirteen-year follow-up of early intervention with an inhaled corticosteroid in patients with asthma.

BACKGROUND: In a 3-year study, adult patients who recently developed asthma (symptoms for less than 1 year) were treated for 2 years with the inhaled corticosteroid (ICS) budesonide (early therapy) or terbutaline. During the third year of the study, terbutaline-treated patients received budesonide (delayed therapy). Differences in lung function and bronchial responsiveness to histamine were observed between the 2 groups. OBJECTIVE: We compared the effects of early versus delayed budesonide therapy after a 10-year follow-up period (13 years after the study began) and current real-life data. METHODS: Of the original 103 patients, 90 were re-examined 13 years after study initiation. After the third year of the study, all patients had their medications, including the dose of ICS, individually adjusted. RESULTS: After the follow-up period, lung function was within the normal range for the entire group (all patients); bronchial responsiveness significantly improved compared with baseline data. No statistically significant differences in clinical or functional variables were found between patients given early or delayed budesonide therapy. However, the delayed therapy group had a higher neutrophil count and higher concentrations of eosinophilic cationic protein and myeloperoxidase in induced sputum. This group had also used more asthma medication and hospital days. CONCLUSIONS: Patients with relatively mild asthma who received ICS within 12 months of their first asthma symptoms or after a 2-year delay achieved equally good functional control of asthma after 10 years of individualized therapy. However, the delayed therapy group exhibited slightly less optimal disease control and more signs of airway inflammation.

Persistence of oxidant and protease burden in the airways after smoking cessation.

BACKGROUND: Oxidative stress is associated with the pathogenesis of cigarette smoke related lung diseases, but longitudinal effects of smoking cessation on oxidant markers in the airways are unknown. METHODS: This study included 61 smokers; 21 with chronic bronchitis or COPD, 15 asthmatics and 25 asymptomatic smokers followed up for 3 months after smoking cessation. Fractional exhaled nitric oxide (FeNO), sputum neutrophil counts, sputum 8-isoprostane, nitrotyrosine and matrix metalloproteinase-8 (MMP-8) were investigated at baseline and 1 and 3 months after smoking cessation. RESULTS: After 3 months 15 subjects had succeeded in quitting of smoking and in these subjects symptoms improved significantly. Unexpectedly, however, sputum neutrophils increased (p = 0.046) after smoking cessation in patients with chronic bronchitis/COPD. At baseline, the other markers did not differ between the three groups so these results were combined for further analysis. Sputum 8-isoprostane declined significantly during the follow-up at 3 months (p = 0.035), but levels still remained significantly higher than in non-smokers. The levels of FeNO, nitrotyrosine and MMP-8 did not change significantly during the 3 months after smoking cessation. CONCLUSION: Whilst symptoms improve after smoking cessation, the oxidant and protease burden in the airways continues for months.

The use of microspirometry in detecting lowered FEV1 values in current or former cigarette smokers.

AIMS: COPD is an underdiagnosed disease. This study was undertaken to assess the value of microspirometry in detecting reduced FEV1 values in cigarette smokers, i.e., subjects at high risk for COPD. METHODS: A total of 611 smokers or ex-smokers with a smoking history >20 years and no previously-diagnosed lung disease were recruited (389 male, age 27-83 years, mean age 56 years, mean smoking history 35 pack years, 19% ex-smokers). RESULTS: An FEV1 < 80% predicted on microspirometry was found in 44.6% of cases. The mean FEV1 was 2.8 litres (80.6% predicted, range 26-121%). This correlated well with values obtained from full spirometry (R=0.965, p<0.0001). Detailed questionnaire responses revealed that almost half of the subjects (48.2%) reported chronic cough and sputum production and 39.8% reported breathlessness during exercise. CONCLUSIONS: Microspirometry finds a considerable number of smokers or ex-smokers with reduced FEV1 values. Microspirometry is quick to perform. All smokers with reduced microspirometry FEV1 values would benefit from smoking cessation, and all patients with reduced FEV1 values need to be considered for full spirometry to confirm if they actually have COPD.

The value of sputum 8-isoprostane in detecting oxidative stress in mild asthma.

BACKGROUND: Exhaled nitric oxide and induced sputum eosinophils are well established as direct markers of inflammation/oxidative stress in asthma. Recently, it has been proposed that sputum 8-isoprostane concentrations may present a reliable index for measuring oxidative stress in asthmatic patients. We assessed the value of sputum 8-isoprostane in mild asthma in children and adolescents. METHODS: Patients with newly diagnosed asthma (children, n = 23; adults, n = 14) and age-matched healthy controls (children, n = 13; adults, n = 15) were studied. Lung function was measured by spirometry, sputum was induced by hypertonic saline, and fractional exhaled nitric oxide (FeNO) was measured with standard methods. Cell differential counts were obtained from sputum slides and the concentration of 8-isoprostane was measured with an enzyme immunoassay from sputum supernatants. RESULTS: High-quality sputum specimens could be obtained from 10 children and 10 adults, and the sputum analyses were conducted only for the representative specimens. Asthmatics had increased FeNO (children 35.5 vs. 11.9 ppb; adults 81.1 vs. 16.6 ppb; p < 0.001) and sputum eosinophils (children 2.4% vs. 1.4%; adults 10.4% vs. 0.2%; p = 0.005) compared to healthy controls. There was a significant correlation between FeNO and eosinophils (R = 0.65; p < 0.0001). Sputum 8-isoprostane was not elevated in asthmatics compared to healthy subjects (children 81.1 vs. 89.9 and adults 76.9 vs. 73.4 pg/mL) and did not correlate with lung function or other measurements of airway inflammation. However, increased 8-isoprostane levels were detected in patients with chronic obstructive pulmonary disease (n = 11, 184.7 pg/mL, used as controls for assays). CONCLUSIONS: In agreement with earlier studies, FeNo is sensitive in detecting oxidative/nitrosative stress in asthmatic airways. However, our results suggest that 8-isoprostane may not be sensitive in reflecting oxidant burden in mild asthma.

Elevated expression and activation of matrix metalloproteinase 8 in tear fluid in atopic blepharoconjunctivitis.

PURPOSE: Matrix metalloproteinase 8 (MMP-8) is an effective collagenolytic enzyme that is associated with many ocular inflammatory diseases, such as uveitis, keratitis, and ocular rosacea. We studied the tear fluid concentration and activation of MMP-8 in atopic blepharoconjunctivitis (ABC) and the presence of the enzyme in conjunctival inflammatory cells in vivo. METHODS: Tear fluid samples were collected from 26 patients with ABC and 26 healthy controls. MMP-8 concentrations were determined by immunofluorometric assay, and its molecular forms and degrees of activation were studied by Western blotting. Conjunctival brush cytology samples from patients with ABC were used for MMP-8 immunocytochemistry. RESULTS: : The mean MMP-8 concentration was statistically significantly higher among the patients with ABC (545.6 +/- 879.3 microg/L) than among the healthy controls (50.4 +/- 62.3 microg/L, P = 0.0001). There was a statistically significant correlation between neutrophils detected in brush cytology and tear fluid MMP-8 (P = 0.032, r = 0.47). Both the control and ABC tear fluid samples contained predominantly the larger (60-80 kDa), highly glycosylated polymorphonuclear leukocyte-type MMP-8 isoform, as identified by Western blotting, but neither was found to contain the mesenchymal-type isoform. The active enzyme was in practice present only in the ABC samples. Immunostainings show the MMP-8 protein to be present in all the main inflammatory cell types within the conjunctiva. CONCLUSIONS: : A higher mean concentration and activation of MMP-8 is present in tear fluid in ABC. This finding probably reflects persistent inflammatory and collagenolytic activity associated with the disease.

Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation.

OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations associated with increased morbidity and mortality. One potential group of enzymes causing tissue destruction in this disease includes neutrophil proteinase elastase (NE), collagenase-2 (matrix metalloproteinase-8 (MMP-8)) and gelatinase B (MMP-9). We investigated the activity of NE and the levels of MMP-8 and MMP-9 in a longitudinal setting at and after COPD exacerbation using a non-invasive technique, i.e., induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation. MATERIAL AND METHODS: The study included healthy non-smokers (n=32), healthy smokers (n=28), patients with stable COPD (n=15), COPD patients with acute exacerbations (exa) (n=10) and their recovery (n=8) after 4 weeks. NE activity by synthetic peptide substrate and spectrophotometry, MMP-8 levels by immunofluorometry and MMP-9 levels by ELISA were analysed from induced sputum supernatants. RESULTS: NE activity and the level of MMP-8 increased highly significantly in patients with COPD exacerbation compared to stable COPD and controls (NE: p = 0.001 and p < 0.0001; MMP-8: p < 0.001 and p < 0.0001). Paired samples showed a decrease of these proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04). The proteinase levels correlated not only with the percentage and number of neutrophils but also with the lung function parameters (FEV1/FVC and diffusion capacity). CONCLUSIONS: COPD exacerbations are associated with neutrophil recruitment into the airways but also transient activation and/or elevation of tissue destruction proteinases, such as NE and MMP-8, which can be detected from the induced sputum supernatants of these COPD patients.

Elevated matrilysin levels in bronchoalveolar lavage fluid do not distinguish idiopathic pulmonary fibrosis from other interstitial lung diseases.

Microarray studies have shown that matrilysin or matrix metalloproteinase (MMP)-7 is highly upregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF), but MMP-7 protein expression has not been systematically compared between IPF and other interstitial lung diseases. MMP-7 levels in bronchoalveolar lavage fluid (BALF) were compared to corresponding samples from nonspecific interstitial pneumonia (NSIP), sarcoidosis, and healthy controls. MMP-7 levels in the BALF were determined by ELISA and localization of MMP-7 in the lung tissue by immunohistochemistry. MMP-7 was similarly elevated in the BALF of all these disorders compared to healthy controls (p=0.007). Even control subjects with prolonged cough displayed a tendency towards elevated MMP-7 expression. There was a negative correlation between BALF MMP-7 levels and forced expiratory vital capacity (r=-0.348, p=0.02, n=42). In IPF lung, MMP-7 immunoreactivity appeared predominantly in the fibrotic parenchyma and arterial wall. In sarcoidosis and NSIP, prominent MMP-7 immunoreactivity was found in areas of inflammation. These results demonstrate that elevated BALF MMP-7 is not restricted to IPF alone but is also observed in other interstitial lung diseases and cannot be used as a differential diagnostic marker for IPF.

Glutathione S-transferase omega in the lung and sputum supernatants of COPD patients.

BACKGROUND: The major contribution to oxidant related lung damage in COPD is from the oxidant/antioxidant imbalance and possibly impaired antioxidant defence. Glutathione (GSH) is one of the most important antioxidants in human lung and lung secretions, but the mechanisms participating in its homeostasis are partly unclear. Glutathione-S-transferase omega (GSTO) is a recently characterized cysteine containing enzyme with the capability to bind and release GSH in vitro. GSTO has not been investigated in human lung or lung diseases. METHODS: GSTO1-1 was investigated by immunohistochemistry and Western blot analysis in 72 lung tissue specimens and 40 sputum specimens from non-smokers, smokers and COPD, in bronchoalveolar lavage fluid and in plasma from healthy non-smokers and smokers. It was also examined in human monocytes and bronchial epithelial cells and their culture mediums in vitro. RESULTS: GSTO1-1 was mainly expressed in alveolar macrophages, but it was also found in airway and alveolar epithelium and in extracellular fluids including sputum supernatants, bronchoalveolar lavage fluid, plasma and cell culture mediums. The levels of GSTO1-1 were significantly lower in the sputum supernatants (p = 0.023) and lung homogenates (p = 0.003) of COPD patients than in non-smokers. CONCLUSION: GSTO1-1 is abundant in the alveolar macrophages, but it is also present in extracellular fluids and in airway secretions, the levels being decreased in COPD. The clinical significance of GSTO1-1 and its role in regulating GSH homeostasis in airway secretions, however, needs further investigations.