Predicting parameters of airway dynamics generated from inspiratory and expiratory plethysmographic airway loops, differentiating subtypes of chronic obstructive diseases.

BACKGROUND: The plethysmographic shift volume-flow loop (sRaw-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective specific airway resistance (sReff), calculated from the ratio of the integral of the resistive aerodynamic specific work of breathing (sWOB) and the integral of the corresponding flow-volume loop. However, computing the inspiratory and expiratory areas of the sRaw-loop separately permits the determination of further parameters of airway dynamics. Therefore, we aimed to define the discriminating diagnostic power of the inspiratory and expiratory sWOB (sWOBin, sWOBex), as well as of the inspiratory and expiratory sReff (sReff IN and sReff EX), for discriminating different functional phenotypes of chronic obstructive lung diseases. METHODS: Reference equations were obtained from measurement of different databases, incorporating 194 healthy subjects (35 children and 159 adults), and applied to a collective of 294 patients with chronic lung diseases (16 children with asthma, aged 6-16 years, and 278 adults, aged 17-92 years). For all measurements, the same type of plethysmograph was used (Jaeger Würzburg, Germany). RESULTS: By multilinear modelling, reference equations of sWOBin, sWOBex, sReff IN and sReff EX were derived. Apart from anthropometric indices, additional parameters such as tidal volume (VT), the respiratory drive (P0.1), measured by means of a mouth occlusion pressure measurement 100 ms after inspiration and the mean inspiratory flow (VT/TI) were found to be informative. The statistical approach to define reference equations for parameters of airway dynamics reveals the interrelationship between covariants of the actual breathing pattern and the control of breathing. CONCLUSIONS: We discovered that sWOBin, sWOBex, sReff IN and sReff EX are new discriminating target parameters, that differentiate much better between chronic obstructive diseases and their subtypes, especially between chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO), thus strengthening the concept of precision medicine.

Assessment of functional diversities in patients with Asthma, COPD, Asthma-COPD overlap, and Cystic Fibrosis (CF).

The objectives of the present study were to evaluate the discriminating power of spirometric and plethysmographic lung function parameters to differenciate the diagnosis of asthma, ACO, COPD, and to define functional characteristics for more precise classification of obstructive lung diseases. From the databases of 4 centers, a total of 756 lung function tests (194 healthy subjects, 175 with asthma, 71 with ACO, 78 with COPD and 238 with CF) were collected, and gradients among combinations of target parameters from spirometry (forced expiratory volume one second: FEV1; FEV1/forced vital capacity: FEV1/FVC; forced expiratory flow between 25-75% FVC: FEF25-75), and plethysmography (effective, resistive airway resistance: sReff; aerodynamic work of breathing at rest: sWOB), separately for in- and expiration (sReffIN, sReffEX, sWOBin, sWOBex) as well as static lung volumes (total lung capacity: TLC; functional residual capacity: FRCpleth; residual volume: RV), the control of breathing (mouth occlusion pressure: P0.1; mean inspiratory flow: VT/TI; the inspiratory to total time ratio: TI/Ttot) and the inspiratory impedance (Zinpleth = P0.1/VT/TI) were explored. Linear discriminant analyses (LDA) were applied to identify discriminant functions and classification rules using recursive partitioning decision trees. LDA showed a high classification accuracy (sensitivity and specificity > 90%) for healthy subjects, COPD and CF. The accuracy dropped for asthma (~70%) and even more for ACO (~60%). The decision tree revealed that P0.1, sRtot, and VT/TI differentiate most between healthy and asthma (68.9%), COPD (82.1%), and CF (60.6%). Moreover, using sWOBex and Zinpleth ACO can be discriminated from asthma and COPD (60%). Thus, the functional complexity of obstructive lung diseases can be understood, if specific spirometric and plethysmographic parameters are used. Moreover, the newly described parameters of airway dynamics and the central control of breathing including Zinpleth may well serve as promising functional marker in the field of precision medicine.

Effects of EPs 7630 on the duration of inability to work in acute bronchitis - a meta-analysis.

Background: Acute bronchitis (AB) has an enormous economic impact through lost working time. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce the time of inability to work. Methods: A meta-analysis of double-blind, randomized, placebo-controlled trials with adult patients suffering from AB was performed. The average number of days of inability to work and the proportion of patients who were still unable to work after one week's treatment were assessed. Results: Four clinical trials with a total of 1,011 evaluable patients who received the marketed dosage of EPs 7630 (n=505) or placebo (n=506) for seven days were included in the meta-analysis. At baseline, 845/1,011 patients (83.6%) were unable to work. In the four trials, the proportion decreased to between 19 and 14% for EPs 7630 and to between 41 and 55% for placebo (meta-analysis risk ratio and 95% confidence interval: 0.35; 0.26-0.45; p<0.001). For the number of sick days, a weighted mean difference of 1.73 days (1.17-2.29 days; p<0.001) favoring EPs 7630 was observed. Conclusions: For adults suffering from AB, this meta-analysis demonstrates that seven days' treatment with Pelargonium sidoides extract EPs 7630 significantly reduces the average number of sick days and significantly increases the proportion of patients who are able to return to work.

Functional Predictors Discriminating Asthma-COPD Overlap (ACO) from Chronic Obstructive Pulmonary Disease (COPD).

Background: A significant proportion of patients with obstructive lung disease have clinical and functional features of both asthma and chronic obstructive pulmonary disease (COPD), referred to as the asthma-COPD overlap (ACO). The distinction of these phenotypes, however, is not yet well-established due to the lack of defining clinical and/or functional criteria. The aim of our investigations was to assess the discriminating power of various lung function parameters on the assessment of ACO. Methods: From databases of 4 pulmonary centers, a total of 540 patients (231 males, 309 females), including 372 patients with asthma, 77 patients with ACO and 91 patients with COPD, were retrospectively collected, and gradients among combinations of explanatory variables of spirometric (FEV1, FEV1/FVC, FEF25-75), plethysmographic (sReff, sGeff, the aerodynamic work of breathing at rest; sWOB), static lung volumes, including trapped gases and measurements of the carbon monoxide transfer (DLCO, KCO) were explored using multiple factor analysis (MFA). The discriminating power of lung function parameters with respect to ACO was assessed using linear discriminant analysis (LDA). Results: LDA revealed that parameters of airway dynamics (sWOB, sReff, sGeff) combined with parameters of static lung volumes such as functional residual capacity (FRCpleth) and trapped gas at FRC (VTG FRC) are valuable and potentially important tools discriminating between asthma, ACO and COPD. Moreover, sWOB significantly contributes to the diagnosis of obstructive airway diseases, independent from the state of pulmonary hyperinflation, whilst the diffusion capacity for carbon monoxide (DLCO) significantly differentiates between the 3 diagnostic classes. Conclusion: The complexity of COPD with its components of interaction and their heterogeneity, especially in discrimination from ACO, may well be differentiated if patients are explored by a whole set of target parameters evaluating, interactionally, flow limitation, airway dynamics, pulmonary hyperinflation, small airways dysfunction and gas exchange disturbances assessing specific functional deficits.

Effects of Pelargonium sidoides extract EPs 7630 on acute cough and quality of life - a meta-analysis of randomized, placebo-controlled trials.

Background: Cough is a leading symptom of viral acute respiratory infections such as acute bronchitis (AB) and the common cold (CC), which can be debilitating and may persist for several weeks. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce cough and improve disease-related quality of life (QoL). Methods: We performed a meta-analysis of randomized, placebo-controlled trials investigating the efficacy of EPs 7630 in AB or CC. Efficacy analyses included change from baseline in a cough intensity score, remission of cough, and disease-associated impairments of QoL. Results: Data of 2,195 participants from 11 trials (3 in children/adolescents with AB, 3 in adults with AB, 5 in adults with CC) were eligible. In children/adolescents with AB, 79.6% of participants treated with EPs 7630 and 41% treated with placebo showed a reduction in the intensity of cough by at least 50% of baseline values at day 7 [meta-analysis rate/risk ratio (RR), EPs 7630 / placebo: 1.86 (95% CI: 1.34; 2.95)], and 18.0% vs 5.5% presented with complete remission of cough [RR: 2.91 (95% CI: 1.26; 6.72)]. In adults with AB, 88.7% of participants in the EPs 7630 group and 47.6% in the placebo group showed a ≥50% response for cough intensity [RR: 2.13 (95% CI: 1.37; 3.31)], while 26.0% vs 6.3% did not cough any more at day 7 [RR: 5.00 [95% CI: 3.10; 8.07)]. Cough scale results were supported by significant improvements over placebo in the pursuit of normal daily activities and other QoL measures. In CC, 56.8% of participants treated with EPs 7630 and 38.8% treated with placebo showed a ≥50% cough intensity reduction [RR: 1.40 (95% CI: 1.19; 1.65)] at day 5, while 26.1% versus 18.4% showed complete remission of cough for EPs 7630 and placebo, respectively [RR: 1.40 (95% CI: 1.06; 1.84)]. CCassociated pain/discomfort and impairment of usual activities were no longer present in 41.5% and 48.8% of participants treated with EPs 7630 compared to less than 40% of patients in the placebo group. Conclusions: The results show that EPs 7630 reduces the burden and leads to earlier remission of cough. Advantages for EPs 7630 were also reflected in self-rated measures of disease-associated QoL. Of note, patients treated with the herbal product felt able to resume their usual daily activities sooner.

Liver Involvement in Acute Respiratory Infections in Children and Adolescents - Results of a Non-interventional Study.

Background: In children and adults with acute respiratory tract infections (ARTI), elevations of serum liver enzyme activities are frequently observed in clinical practice. However, epidemiological data particularly in the pediatric population are very limited. The aim of this study was to assess the incidence of hepatic involvement, to identify the viruses and to analyze risk factors in children and adolescents with ARTI in a real-world setting. Methods: We report on a prospective, multicenter, non-interventional study with 1,010 consecutive patients aged 1-17 years with ARTI who consulted a physician within 5 days after onset of symptoms. Laboratory blood tests and PCR virus detection in nasopharyngeal lavage were performed at first presentation and after 3-7 days. Patients with elevated activities of serum liver enzymes (ASAT, ALAT, and γ-GT) were determined in local laboratories and values were normalized by dividing by the individual upper limit of the normal range (ULN). The resulting index (<1 means below ULN, >1 means above ULN) allowed to compare results from laboratories with different reference ranges. Results: Laboratory test results of 987 patients were available at first visit. 11.1% (95% CI: 9.2-13.3%) exhibited an elevation of ASAT, ALAT, and/or γ-GT activities. Virus DNA or RNA was identified in nasopharyngeal lavages of 63% of the patients. 12.2% of patients with positive PCR and 9.7% of those with negative PCR (p = 0.25) had elevated serum liver enzyme activities. The highest rates were observed in patients with a positive result for influenza B virus (24.4%) followed by human metapneumovirus (14.6%), and human coronavirus (others than SARS-CoV-2) (13.6%). The rate of children and adolescents with ARTI and elevation of serum liver enzyme activities correlated with the virus species and with overweight of the patients but did not differ in patients with or without previous medication intake. Conclusion: Elevated enzyme activities are present in about 10% of children and adolescents with ARTI. In our cohort, these elevations were mild to moderate; probably resulting from an inflammation process with hepatic involvement.

Normative reference equations of airway dynamics assessed by whole-body plethysmography during spontaneous breathing evaluated in infants, children, and adults.

Effective specific airway resistance (sReff ), its reciprocal the effective specific airway conductance (sGeff ) are computed as ratios between the integral of the resistive aerodynamic work of breathing (sWOB) and the integral of the tidal flow/volume loop, the reciprocal, respectively. Unfortunately, reference equations to obtain normative values for sReff , sGeff , and sWOB are not yet available. To assess reference equations for sWOB, sReff , and sGeff during tidal breathing at resting level in healthy infants, children, and adults by a multidimensional model. Retrospectively exported data were collected from databases of five Swiss lung function centers, in which plethysmography (Jaeger Würzburg, Germany) was performed for the assessment of airway dynamics, static lung volumes, and forced breathing flow-volume loops, in a collective of 28 healthy infants, 47 children, and 273 adults. From this cohort, reference equations were computed based on anthropometric measures, lung volumes, indices of the breathing pattern, and timing of breathing. By multi-linear modeling reference equations of sReff , sGeff , and sWOB could be defined taking as independent parameters apart from anthropometric parameters, also parameters given by the ratio between the tidal volume and functional residual capacity (FRCpleth /VT ), and the ratio between VT and inspiratory time (VT /TI ). An alternative statistical approach to define reference equations of airway dynamics reveals that apart from the subject's anthropometric measurements, parameters of the magnitude of static lung volumes, the breathing pattern, and the timing of breathing are co-variants of reference equations of airway dynamics over a large age range.

Validation of a Clinical Instrument for Measuring the Severity of Acute Bronchitis in Children - The BSS-ped.

BACKGROUND: There are no validated standardised clinical procedures for severity measurement of acute bronchitis in children. The "BSS-ped", a short version of the physician-rated assessment scale BSS (Bronchitis Severity Scale), can fill this gap, if it is valid. OBJECTIVE: To examine the scale´s validity. METHODS: Investigations were planned according to classical clinical-psychometric validity criteria including a formal competence evaluation of the scale´s authors and statistical analyses of data from 78 patients aged 1-6 and diagnosed with "acute bronchitis". Cross-validation was provided by analysis of data from 70 children with matching age, sex and diagnosis. All children were examined three times (day 0, 3-5 and 7) using the BSS-ped in addition to other clinical and psychometric monitoring procedures. RESULTS: The evidently high level of expertise of the scale's authors substantiates pronounced content validity and relevance of the BSS-ped and its items. The validity criterion, i.e. to reflect the unidimensional severity of acute bronchitis and its change using the BSS-ped score, was fulfilled. There were substantial correlations with other scales measuring the current health-related quality of life, as well as satisfaction and success of treatment. Severity change prognoses for acute bronchitis under placebo and an active substance were correct. The BSS-ped was found to be a feasible instrument because it can be repeated at short intervals (minute range) without any special technical aids or extended training. CONCLUSION: The BSS-ped is a valid procedure for measuring the severity of acute bronchitis in children.

Pelargonium sidoides preparation EPs 7630 in COPD: health-related quality-of-life and other patient-reported outcomes in adults receiving add-on therapy.

OBJECTIVE: Patient-reported outcomes (PRO) such as health-related quality-of-life (HRQoL) belong to the most important criteria for the evaluation of medical therapies in clinical trials or practice-based benefit assessments. This study, therefore, revisited results of an earlier published clinical trial investigating the effects of the herbal drug preparation from the roots of Pelargonium sidoides EPs 7630, administered as add-on therapy in patients suffering from chronic obstructive pulmonary disease (COPD), with respect to HRQoL and other PRO. METHODS: A total of 199 adults diagnosed with COPD stages II/III and receiving standard treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were randomly assigned to add-on therapy with EPs 7630 or placebo for 24 weeks. HRQoL (disease-specific St. George's Respiratory Questionnaire, SGRQ; current HRQoL state according to the EuroQuol visual analog scale, EQ VAS) and PRO (Integrative Medicine Outcomes Scale, IMOS; Integrative Medicine Patient Satisfaction Scale, IMPSS; symptom severity score of cough, sputum production and sternal pain while coughing; duration of inability to work) were assessed at each study visit or documented daily by the patient in a patient diary, respectively. RESULTS: At week 24, all HRQoL and PRO measures showed a more pronounced improvement under EPs 7630 than under placebo (EQ VAS, p < .001; SGRQ total score, p < .001; symptom severity score of cough, sputum production, and sternal pain while coughing, p = .021; duration of inability to work, p = .004; two-sided t-test each; IMOS, p < .001, IMPSS, p < .001, two-sided Mantel-Haenszel test each). Moreover, the difference seen for the SGRQ exceeded the SGRQ minimal clinically important difference (MCID) threshold of 4 points. CONCLUSIONS: Add-on therapy with EPs 7630 led to an improvement in HRQoL and other PRO in adult patients with COPD compared to placebo while showing a good long-term tolerability.

Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD.

BACKGROUND: Preventing and managing exacerbations is one major component in COPD treatment. We investigated whether EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides, could prolong time to acute exacerbation in patients with COPD stage II/III. METHODS: In this randomised, double-blind, placebo-controlled clinical trial, patients were randomly allocated to oral 24-week add-on therapy with 3 × 30 drops/day EPs 7630 (n = 99) or placebo (n = 101) to a standardised baseline-treatment. Primary endpoint was time to first exacerbation of COPD. Secondary endpoints were number of exacerbations, consumption of antibiotics, quality of life, patient satisfaction, inability to work, and tolerability. RESULTS: Median time to exacerbation was significantly prolonged with EPs 7630 compared to placebo (57 versus 43 days, Kaplan-Maier-estimate; p = 0.005, one-sided centre-stratified log-rank test). The superiority of EPs 7630 was also confirmed in secondary endpoints, e.g., fewer exacerbations, less patients with antibiotic use, improved quality of life, higher patient satisfaction, and less days of inability to work. The incidence of minor gastrointestinal adverse events was higher in the EPs 7630 group. CONCLUSIONS: The results demonstrate a statistically significant and clinically relevant superiority of add-on therapy with EPs 7630 over placebo and a good long-term tolerability in the treatment of moderate to severe COPD. EPs 7630 prolonged time to exacerbations and reduced exacerbation frequency and antibiotic use. Trial Registration No.: ISRCTN01681733.

Fit for high altitude: are hypoxic challenge tests useful?

Altitude travel results in acute variations of barometric pressure, which induce different degrees of hypoxia, changing the gas contents in body tissues and cavities. Non ventilated air containing cavities may induce barotraumas of the lung (pneumothorax), sinuses and middle ear, with pain, vertigo and hearing loss. Commercial air planes keep their cabin pressure at an equivalent altitude of about 2,500 m. This leads to an increased respiratory drive which may also result in symptoms of emotional hyperventilation. In patients with preexisting respiratory pathology due to lung, cardiovascular, pleural, thoracic neuromuscular or obesity-related diseases (i.e. obstructive sleep apnea) an additional hypoxic stress may induce respiratory pump and/or heart failure. Clinical pre-altitude assessment must be disease-specific and it includes spirometry, pulsoximetry, ECG, pulmonary and systemic hypertension assessment. In patients with abnormal values we need, in addition, measurements of hemoglobin, pH, base excess, PaO2, and PaCO2 to evaluate whether O2- and CO2-transport is sufficient.Instead of the hypoxia altitude simulation test (HAST), which is not without danger for patients with respiratory insufficiency, we prefer primarily a hyperoxic challenge. The supplementation of normobaric O2 gives us information on the acute reversibility of the arterial hypoxemia and the reduction of ventilation and pulmonary hypertension, as well as about the efficiency of the additional O2-flow needed during altitude exposure. For difficult judgements the performance of the test in a hypobaric chamber with and without supplemental O2-breathing remains the gold standard. The increasing numbers of drugs to treat acute pulmonary hypertension due to altitude exposure (acetazolamide, dexamethasone, nifedipine, sildenafil) or to other etiologies (anticoagulants, prostanoids, phosphodiesterase-5-inhibitors, endothelin receptor antagonists) including mechanical aids to reduce periodical or insufficient ventilation during altitude exposure (added dead space, continuous or bilevel positive airway pressure, non-invasive ventilation) call for further randomized controlled trials of combined applications.

[Pelargonium sidoides in acute bronchitis - Health-related quality of life and patient-reported outcome in adults receiving EPs 7630 treatment]. / Pelargonium sidoides bei akuter Bronchitis - Gesundheitsbezogene Lebensqualität und Therapiebeurteilung aus Patientensicht unter Behandlung mit EPs 7630.

Health-related quality of life (HRQL) and patient-reported outcome (PRO) have become important outcome parameters for the evaluation of medical treatment within clinical trials and, furthermore, to evaluate efficiency in clinical practice. We therefore report further exploratory results of an already reported dose-finding study with EPs 7630 tablets, now focussing on HRQL and PRO. A total of 406 adults with acute bronchitis were randomly assigned to one of four parallel treatment groups (placebo, 30 mg, 60 mg or 90 mg EPs 7630 daily). HRQL and PRO were assessed by questionnaires as secondary outcome measures at each study visit or daily in the patient's diary. At day 7, the patient-reported outcome measures were significantly more improved in all the three EPs 7630 groups compared to placebo (EQ-5D and EQ VAS, SF-12: physical score, impact of patient's sickness, duration of activity limitation, patient-reported treatment outcome, satisfaction with treatment). In conclusion, a statistically significant and clinically relevant improvement of HRQL/PRO compared to placebo was shown in all the three EPs 7630 groups.

EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomised, double-blind, placebo-controlled, multicentre trial.

Acute bronchitis commonly associated with cough is predominantly caused by viral infections. The burden on health-care systems and society is enormous. A randomised, placebo-controlled, multicentre clinical trial to investigate the efficacy and safety of a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) was conducted in 217 adult outpatients with acute bronchitis. The primary efficacy variable was the bronchitis symptom score (BSS) ranging from 0 to 20. Primary data of this study were already published in 2007. Now, we present further analyses of these already published data combined with new results in order to focus on both the most important features of acute bronchitis and pharmaco-economic aspects of the disease. The BSS decreased by 7.6 +/- 2.2 (mean +/- SD) points for the active treatment group and 5.3 +/- 3.2 points for placebo (p < 0.0001). As compared with placebo, a marked improvement has been shown for EPs 7630 for all disease symptoms (cough, sputum, rales, dyspnoe, pain on coughing, hoarseness, headache, fatigue, fever, limb pain) categorised in severity classes by the patient. Especially strong antitussive and "anti-fatigue" effects with an early onset during treatment were observed. Patients in the EPs 7630 group were sooner able to work and to a lesser extent confined to bed. In both treatment groups, 3 x 30 drops of the trial medication administered for 7 days were well tolerated. No serious adverse events have been observed. In conclusion, EPs 7630 is superior to placebo in the treatment of acute bronchitis and leads to faster remission of bronchitis related symptoms.

Long-term survival of a patient with congenital central hypoventilation syndrome despite the lack of continuous ventilatory support.

Untreated idiopathic congenital central hypoventilation syndrome (CCHS) is thought to cause infant death within 1-2 months. Here we present an adult patient with CCHS who survived without continuous ventilatory support, despite hypoventilation from early childhood onward. The diagnosis was confirmed at the age of 22 years, when the patient presented with hypoventilation during the night (PaCO2 60 mm Hg, PaO2 56 mm Hg, pH 7.32 HCO3- 30 mmol/l) but hyperventilation when awake (PaCO2 26 mm Hg, PaO2 81 mm Hg, pH 7.56, HCO3- 23 mmol/l). The maximal hematocrit was 77%. Despite mental retardation, noninvasive positive pressure ventilation (NPPV) could be successfully established. NPPV-supported ventilation during the night (PaCO2 36, PaO2 84 mm Hg, pH 7.47, HCO3- 25 mmol/l) reduced hematocrit values (40.6 to 36.8%) over a period of 4 years. In conclusion, long-term survival with CCHS is possible without continuous ventilatory support. Spontaneous improvement of hypoventilation during sleep throughout childhood is possible and hyperventilation during wakefulness may occur in patients with CCHS. CCHS can be managed with NPPV despite mental retardation, even over a long-term period.

The Severe Respiratory Insufficiency (SRI) Questionnaire: a specific measure of health-related quality of life in patients receiving home mechanical ventilation.

BACKGROUND AND OBJECTIVE: The objective of this study was to develop a specific instrument for measuring health-related quality of life (HRQL) in patients receiving home mechanical ventilation (HMV). METHODS: The Severe Respiratory Insufficiency (SRI) Questionnaire was developed and tested for its psychometric properties following a multicentric clinical trial including 226 patients receiving HMV (mean age 57.3+/-14.0 years). RESULTS: Forty-nine items passed the selection process and were allocated to seven subscales: Respiratory Complaints, Physical Functioning, Attendant Symptoms and Sleep, Social Relationships, Anxiety, Psychologic Well-Being, and Social Functioning. Cronbach's alpha was >0.7 in all subscales and >0.8 in four subscales indicating high internal consistency reliability. Construct validity was confirmed by factor analysis, indicating one summary scale that accounts for 59.8% of the variance. Concurrent validity was confirmed by correlating subscales of the SRI and the SF-36 (0.21

Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial.

BACKGROUND: New evidence-based treatment options are required to avoid antibiotic overuse in acute bronchitis and to replace potentially inefficacious initial antibiotic treatment. OBJECTIVE: To evaluate the efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) compared to placebo in patients with acute bronchitis. DESIGN: Randomized, double-blind, placebo-controlled trial using a multi-stage adaptive design. SETTING: 36 primary care physicians (investigators) at the out-patient care setting. PATIENTS: 468 adults with acute bronchitis present < or = 48 hours, Bronchitis Severity Score (BSS) > or = 5 points, and informed consent. INTERVENTION: EPs 7630 or placebo (30 drops three times daily) for 7 days. MEASUREMENT: The primary outcome criterion was the change of BSS on day 7. RESULTS: The decrease of BSS from baseline to day 7 was 5.9 +/- 2.9 points under EPs 7630 (n = 233), and 3.2 +/- 4.1 points under placebo (n = 235). The 95% CI for the difference of effects between the two treatment groups (EPs 7630 minus placebo) was calculated as [-3.359; -2.060] showing a significant superiority of EPs 7630 compared to placebo on day 7 (p < 0.0001). Working inability decreased to 16% in the EPs 7630 group compared to 43% in the placebo group (p < 0.0001). In addition, the duration of illness was significantly shorter for patients treated with EPs 7630 compared to placebo (p < 0.001). Within the first four days, onset of treatment effect was recognized in 53.6% of patients under EPs 7630 compared to 36.2% of patients under placebo, only (p < 0.0001). Adverse events (AEs) occurred in 36/468 patients (EPs 7630: 20/233 patients, placebo: 16/235 patients). All events were assessed as non-serious. CONCLUSION: EPs 7630 was superior in efficacy compared to placebo in the treatment of adults with acute bronchitis. Treatment with EPs 7630 clearly reduced the severity of symptoms and shortened the duration of working inability for nearly 2 days.

Evaluation of health-related quality of life using the MOS 36-Item Short-Form Health Status Survey in patients receiving noninvasive positive pressure ventilation.

OBJECTIVE: To collect benchmark data on the MOS 36-Item Short-Form Health Status Survey (SF-36) in patients receiving noninvasive positive pressure ventilation and to examine whether health-related quality of life is influenced by the underlying disease or by physical parameters. DESIGN AND SETTING: Multicentric clinical cross-sectional trial in four general wards specialized in noninvasive positive pressure ventilation. PATIENTS AND PARTICIPANTS: 226 patients (78 chronic obstructive pulmonary disease, 57 kyphoscoliosis, 20 posttuberculosis sequelae, 17 Duchenne muscular dystrophy, 13 polyneuropathy, 13 myopathy, 6 amyotrophic lateral sclerosis, 12 obesity-hypoventilation syndrome, 4 poliomyelitis sequelae, 3 phrenic nerve lesion, 3 central hypoventilation syndrome) who used noninvasive positive pressure ventilation for home mechanical ventilation. MEASUREMENTS AND RESULTS: Health-related quality of life as assessed by the SF-36 was lower than in the general population. Overall the Physical Component Summary (PCS) was significantly lower than the general population norm; the Mental Component Summary (MCS) was also reduced but less markedly. Patients with chronic obstructive pulmonary disease were more impaired in MCS than those with kyphoscoliosis. PCS was significantly associated with age. Gender, lung function, and arterial blood gas values were not significant predictors of health-related quality of life. CONCLUSIONS: Benchmark SF-36 data in patients receiving noninvasive positive pressure ventilation are given. Although physical health is significantly impaired in these patients, this does not necessarily lead to mental limitation, and mental health is influenced by the underlying disease, but not by physical parameters.

Weaning from mechanical ventilation by long-term nasal positive pressure ventilation in two patients with acute respiratory distress syndrome associated with pneumococcal sepsis.

Only few data concerning weaning by nasal positive pressure ventilation (NPPV) are available, and successful weaning by using NPPV in patients with acute respiratory distress syndrome (ARDS) and severe complications has not yet been described. Two cases with ARDS and both preexisting thoracopulmonary disease (infundibulum abnormality and suspected COPD) and associated complications (recurrent sepsis, acute renal failure, need for lobectomy, severe malnutrition) could not be weaned by invasive ventilatory techniques. Both patients presented with rapid shallow breathing and PaCO(2) values >60 mm Hg during intermittent trials of spontaneous breathing, although the primary pathology and associated complications had been resolved. Patients were successfully adapted on NPPV in a stepwise approach after 93 days and 67 days of invasive ventilation. In one patient withdrawal from NPPV was possible after 2 months. In the other patient the duration of daily ventilation could be significantly reduced from 18 to 6 h/day after 9 months on NPPV. Therefore, patients with ARDS who cannot be weaned by invasive ventilatory strategies might be removed successfully from invasive mechanical ventilation by using NPPV even when there are preexisting thoracopulmonary disease and major complications during invasive ventilation.