TY  - JOUR
AB  - INTRODUCTION: Interstitial lung diseases (ILDs) are associated with a high economic burden, yet prospective data of the German healthcare system are sparse. OBJECTIVE: We assessed average ILD-related costs of pharmacological and non-pharmacological (hospitalizations, outpatient, rehabilitation, physiotherapy, and medical aids) interventions in ILD. METHODS: We used data from the multicenter, observational, prospective Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases registry to evaluate adjusted per capita costs and cost drivers for ILD-related healthcare costs over 4 years, using generalized estimating equation regression models. RESULTS: Idiopathic pulmonary fibrosis (IPF) had the highest annual pharmacological costs >EUR 21,000, followed by connective tissue disease-associated ILD (CTD-ILD) averaging EUR 6,000. Other idiopathic interstitial pneumonias and hypersensitivity pneumonitis averaged below EUR 2,400 and sarcoidosis below EUR 400. There were no significant differences in pharmacological costs over time. Trends in non-pharmacological costs were statistically significant. At year 1, CTD-ILD had the highest costs (EUR 7,700), while sarcoidosis had the lowest (EUR 2,547). By year 4, these declined to EUR 3,218 and EUR 232, respectively. Regarding cost drivers, the ILD subtype had the greatest impact with 75 times higher pharmacological costs in IPF and 4 times higher non-pharmacological costs in CTD-ILD, compared to the reference. Pulmonary hypertension (PH) and gastroesophageal reflux disease (GERD) triggered higher pharmacological costs, and higher values of forced vital capacity % predicted were associated with lower pharmacological and non-pharmacological costs. CONCLUSION: Stabilizing lung function and reducing the impact of PH and GERD are crucial in reducing the economic burden of ILD. There is an urgent need for effective treatment options, especially in CTD-ILD.
AU  - Maqhuzu, P.N.
AU  - Schwarzkopf, L.
AU  - Markart, P.*
AU  - Behr, J.*
AU  - Holle, R.
AU  - Leidl, R.
AU  - Kreuter, M.*
C1  - 66628
C2  - 53256
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 1015-1023
TI  - Costs of pharmacological and non-pharmacological interventions in interstitial lung disease management in Germany.
JO  - Respiration
VL  - 101
IS  - 11
PB  - Karger
PY  - 2022
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Background: Patients with COPD-specific symptoms and history but FEV1/FVC ratio ≥0.7 are a heterogeneous group (former GOLD grade 0) with uncertainties regarding natural history. Objective: We investigated which lung function measures and cutoff values are predictive for deterioration according to GOLD grades and all-cause mortality. Methods: We used visit 1-4 data of the COSYCONET cohort. Logistic and Cox regression analyses were used to identify relevant parameters. GOLD 0 patients were categorized according to whether they maintained grade 0 over the following 2 visits or deteriorated persistently into grades 1 or 2. Their clinical characteristics were compared with those of GOLD 1 and 2 patients. Results: Among 2,741 patients, 374 GOLD 0, 206 grade 1, and 962 grade 2 patients were identified. GOLD 0 patients were characterized by high symptom burden, comparable to grade 2, and a restrictive lung function pattern; those with FEV1/FVC above 0.75 were unlikely to deteriorate over time into grades 1 and 2, in contrast to those with values between 0.70 and 0.75. Regarding mortality risk in GOLD 0, FEV1%predicted and age were the relevant determinants, whereby a cutoff value of 65% was superior to that of 80% as proposed previously. Conclusions: Regarding patients of the former GOLD grade 0, we identified simple criteria for FEV1/FVC and FEV1% predicted that were relevant for the outcome in terms of deterioration over time and mortality. These criteria might help to identify patients with the typical risk profile of COPD among those not fulfilling spirometric COPD criteria.
AU  - Mayerhofer, B.*
AU  - Jörres, R.A.*
AU  - Lutter, J.
AU  - Waschki, B.*
AU  - Kauffmann-Guerrero, D.*
AU  - Alter, P.*
AU  - Trudzinski, F.C.*
AU  - Herth, F.J.F.*
AU  - Holle, R.*
AU  - Behr, J.*
AU  - Bals, R.*
AU  - Welte, T.*
AU  - Watz, H.*
AU  - Vogelmeier, C.F.*
AU  - Kahnert, K.*
C1  - 61168
C2  - 50091
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 308-317
TI  - Deterioration and mortality risk of COPD patients not fitting into standard GOLD categories: Results of the COSYCONET Cohort.
JO  - Respiration
VL  - 100
IS  - 4
PB  - Karger
PY  - 2021
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Background: Diabetes mellitus is a significant comorbidity of interstitial lung disease (ILD). Objectives: The aim of this study was to investigate the incidence of restrictive lung disease (RLD) and ILD in patients with prediabetes and type 2 diabetes (T2D). Methods: Forty-eight nondiabetics, 68 patients with prediabetes, 29 newly diagnosed T2D, and 110 patients with long-term T2D were examined for metabolic control, diabetes-related complications, breathlessness, and lung function. Five participants with T2D, breathlessness, and RLD underwent multidetector computed tomography (MDCT) and a Six-Minute Walk Test (6MWT). Lung tissue from 4 patients without diabetes and from 3 patients with T2D was histologically examined for presence of pulmonary fibrosis. Results: Breathlessness in combination with RLD was significantly increased in patients with prediabetes and T2D (p < 0.01). RLD was found in 9% of patients with prediabetes, in 20% of patients with newly diagnosed T2D, and in 27% of patients with long-term T2D. Thus, patients with long-term T2D had an increased risk of RLD (OR 5.82 [95% CI 1.71-20.5], p < 0.01). RLD was significantly associated with glucose metabolism and albuminuria (p < 0.01); furthermore, presence of nephropathy increased the risk of RLD (OR 8.57 [95% CI 3.4-21.9], p < 0.01) compared to nondiabetics. MDCT revealed ILD in 4 patients, the 6MWT correlated with the extent of ILD, and histological analysis showed fibrosing ILD in patients with T2D. Conclusions: This study demonstrates increased breathlessness and a high prevalence of RLD in patients with T2D, indicating an association between diabetes and fibrosing ILD.
AU  - Kopf, S.*
AU  - Groener, J.B.*
AU  - Kender, Z.*
AU  - Fleming, T.*
AU  - Brune, M.*
AU  - Riedinger, C.*
AU  - Volk, N.*
AU  - Herpel, E.*
AU  - Pesta, D.*
AU  - Szendroedi, J.*
AU  - Wielpuetz, M.O.*
AU  - Kauczor, H.U.*
AU  - Katus, H.A.*
AU  - Kreuter, M.*
AU  - Nawroth, P.P.
C1  - 54106
C2  - 45315
CY  - Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
SP  - 29-40
TI  - Breathlessness and restrictive lung disease: AniImportant diabetes-related feature in patients with type 2 diabetes.
JO  - Respiration
VL  - 96
IS  - 1
PB  - Karger
PY  - 2018
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Background: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis(IPF) and has been shown to slow disease progression by reducing annual lung function decline. Objective: To evaluate the results of a large cohort of IPF patients treated with nintedanib within a compassionate use program(CUP) in Germany(9 centers). Methods: Patients ( >= 40 years) were required to have a confirmed diagnosis of IPF, a forced vital capacity(FVC) >= 50% predicted ( pred.) and a carbon monoxide diffusing capacity(DLCO) 30-79% pred. and not to be eligible for pirfenidone treatment. Clinical data, pulmonary function tests and adverse events were recorded up to July 2015. Results: Sixty-two patients (48 male/14 female) with moderate IPF (FVC 64 +/- 17% pred. and DLCO 40 +/- 10% pred.) were treated with nintedanib. 77% of patients switched from pirfenidone (mean treatment duration 14 +/- 2 months) mostly due to disease progression (mean decline in FVC 7.4 +/- 3% pred. in the 6 months prior to nintedanib intake). Initiation of nintedanib treatment occurred 69 +/- 29 months after IPF diagnosis, and mean treatment duration was 8 +/- 4 months. Most patients (63%) stabilized 6 months after treatment start (mean FVC decline 3 +/- 1 vs. -17 +/- 2% in patients with disease progression; p < 0.01). The most common adverse events were diarrhea (63%) and weight loss (50%). Dose reduction occurred in 34% of cases and treatment discontinuation in 10%. Conclusion: Nintedanib treatment was generally well tolerated and was associated with FVC stabilization in the majority of IPF patients in this CUP setting where most patients were not treatment naive. Our data are in agreement with the previously published data.
AU  - Bonella, F.*
AU  - Kreuter, M.*
AU  - Hagmeyer, L.*
AU  - German Nintedanib Compassionate Use Consortium (Neurohr, C.
AU  - Milger, K.)
AU  - Keller, C.*
AU  - Kohlhaeufl, M.J.*
AU  - Mueller-Quernheim, J.*
AU  - Prasse, A.*
C1  - 49795
C2  - 42207
CY  - Basel
SP  - 98-106
TI  - Insights from the German compassionate use program of nintedanib for the treatment of idiopathic pulmonary fibrosis.
JO  - Respiration
VL  - 92
IS  - 2
PB  - Karger
PY  - 2016
SN  - 0025-7931
ER  - 

TY  - JOUR
AU  - Burgstaller, G.
C1  - 42904
C2  - 35808
CY  - Basel
SP  - 15-16
TI  - Digging into 'the Rabbit-Hole' of the extracellular matrix.
JO  - Respiration
VL  - 89
IS  - 1
PB  - Karger
PY  - 2015
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Background: The diagnostic use of lung function using spirometry depends on the validity of reference equations. A multitude of spirometric prediction values have been published, but in most of these studies older age groups are underrepresented. Objectives: The aim of the present study was to establish new spirometric reference values for advanced age and to compare these to recent prediction equations from population-based studies. Methods: In the present study spirometry was performed in a population-based sample from the KORA-F4 and KORA-Age cohorts (2006-2009, Augsburg, Germany) comprising 592 never-smoking subjects aged 42-89 years and with no history of respiratory disease. Using quantile regression analysis, equations for the median and lower limit of normal were derived for indices characterizing the expiratory flow-volume curve: forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC, peak expiratory flow (PEF), and forced expiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF(25), FEF(50) and FEF(75)). Results: FEV(1) and FVC were slightly higher, and PEF was lower compared to recently published equations. Importantly, forced expiratory flow rates at middle and low lung volume, as putative indicators of small airway disease, were in good agreement with recent data, especially for older age. Conclusion: Our study provides up-to-date reference equations for all major indices of flow-volume curves in middle and advanced age in a South German population. The small deviations from published equations indicate that there might be some regional differences of lung function within the Caucasian population of advanced age in Europe.
AU  - Karrasch, S.*
AU  - Flexeder, C.
AU  - Behr, J.*
AU  - Holle, R.
AU  - Huber, R.M.*
AU  - Jörres, R.A.*
AU  - Nowak, D.*
AU  - Peters, A.
AU  - Wichmann, H.-E.
AU  - Heinrich, J.
AU  - Schulz, H.
C1  - 8352
C2  - 30070
SP  - 210-219
TI  - Spirometric reference values for advanced age from a South German population.
JO  - Respiration
VL  - 85
IS  - 3
PB  - Karger
PY  - 2013
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations.
AU  - Königshoff, M.
C1  - 5275
C2  - 28683
SP  - 353-358
TI  - Lung cancer in pulmonary fibrosis: Tales of epithelial cell plasticity.
JO  - Respiration
VL  - 81
IS  - 5
PB  - Karger
PY  - 2011
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Chronic inflammatory processes of the airways induced by long-time cigarette consumption are a crucial factor in the pathogenesis of chronic obstructive pulmonary disease. In contrast, the role of cigarette smoking in the pathogenesis of bronchial hyperreactivity (BHR) is still unclear. The aim of this study was to assess the effect of chronic cigarette consumption on pulmonary function tests and BHR in healthy subjects. 63 healthy smokers and 63 lifetime nonsmokers matched for sex, age, height and weight were evaluated. Pulmonary function was determined by body plethysmography and spirometry. Bronchial provocation was performed by inhalation of increasing doses of carbachol (up to 25 g/l) in isotonic NaCl solution. Pulmonary function tests were within normal limits in all subjects. Nevertheless, midexpiratory flow at 25% of forced vital capacity was significantly smaller, and functional residual capacity was significantly greater in middle-aged smokers (age: 40-60 years) compared to middle-aged nonsmokers (p < 0.05, both comparisons). In young smokers and nonsmokers (age: 20-30 years) pulmonary function tests were not different (p > 0.28, all comparisons). Importantly, the carbachol concentration that provoked a 50% rise in specific airway resistance (PD50sRaw) was similar in smokers and nonsmokers of both age groups (p > 0.05, both comparisons) and did not correlate with the age of the subjects (p > 0.2). No correlations between baseline values of pulmonary function tests and PD50sRaw were observed (p > 0.34, all comparisons). The observations confirm that the distribution profile of BHR is unimodal and apparently not affected by age and smoking habits. Cigarette smoking likely has not a determining influence on the development of BHR.
AU  - Siekmeier, R.
AU  - Buhl, R.
AU  - Schultze- Werninghaus, G.
AU  - Kronenberger, H.
C1  - 40039
C2  - 37859
SP  - 199-203
TI  - Unspecific bronchial reactivity to carbachol in healthy subjects - effect of age and smoking habits.
JO  - Respiration
VL  - 61
IS  - 4
PY  - 1994
SN  - 0025-7931
ER  - 

TY  - JOUR
AB  - Bronchoalveolar lavage (BAL) may have a potential role in contributing to a more precise definition of COPD disorders, but at present little is known about the cellular and biochemical changes that occur in BAL in the different stages of COPD. On the contrary, BAL features due to smoking habits, a well-known risk factor for COPD, have been widely investigated. We submitted to BAL 15 normal nonsmokers, 15 asymptomatic smokers and 11 smokers affected by chronic bronchitis. In this latter group BAL fluid recovery was significantly reduced and cellularity increased, but less prominently than in asymptomatic smokers. The CD4/CD8 ratio was significantly decreased in smokers with and without bronchitis, the CD8 percentage being positively correlated with the smoking history. NK cells were decreased in patients with chronic bronchitis. BAL neutrophils were increased in both smoker groups and a correlation was seen with smoking history and degree of airflow obstruction. Neutrophils are markedly involved in the oxidation of BAL proteins, as we could determine with the evaluation of the methionine sulphoxide/methionine ratio in BAL fluids. This finding may be relevant to better understand COPD pathogenesis and progression.
AU  - Costabel, U.
AU  - Maier, K.L.
AU  - Teschler, H.
AU  - Wang, Y.M.
C1  - 18246
C2  - 11463
SP  - 17-19
TI  - Local immune components in chronic obstructive pulmonary disease.
JO  - Respiration
VL  - 59
IS  - 1
PY  - 1990
SN  - 0025-7931
ER  -