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Purpose: COVID-19 causes high mortality in Lung Transplant (LTx) patients, therefore vaccination in this population is potentially life-saving. However, the antibody response is impaired after three vaccinations in LTx patients. We questioned whether this response might be increased, and therefore studied the serological IgG antibody response across up to five doses of the SARS-CoV-2 vaccine. In addition, risk factors for non-response were investigated. Methods: In this large retrospective cohort study, antibody responses were assessed after 1–5 mRNA-based SARS-CoV-2 vaccines in all LTx patients between February 2021 and September 2022. A positive vaccine response was defined as an IgG level ≥ 300 BAU/mL. Positive antibody responses due to COVID-19 infection were excluded from the analysis. Outcome and clinical parameters were compared between responders and non-responders, and multivariable logistic regression analysis was performed to determine the risk factors for vaccine-response failure. Results: The antibody responses of 292 LTx patients were analyzed. Positive antibody response to 1–5 SARS-CoV-2 vaccinations occurred in 0%, 15%, 36%, 46%, and 51%, respectively. During the study period, 146/292 (50%) of the vaccinated individuals tested positive for SARS-CoV-2 infection. The COVID-19-related mortality was 2.7% (4/146), and all four patients were non-responders. Risk factors associated with non-response to SARS-CoV-2 vaccines in univariable analyses were age (p = 0.004), chronic kidney disease (CKD) (p = 0.006), and shorter time since transplantation (p = 0.047). In the multivariable analysis, they were CKD (p = 0.043), and shorter time since transplantation (p = 0.028). Conclusion: A two- to five-dose regime of SARS-CoV-2 vaccines in LTx patients increases the probability of vaccine response and results in a cumulative vaccine response in 51% of the LTx population. LTx patient antibody response to SARS-CoV-2 vaccinations is therefore impaired, especially in patients shortly after LTx, patients with CKD, and the elderly.

Background Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin. Methods Relevant databases were queried and study outcomes extracted using a standardized method and summarized. Results Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0–3%), but CLAD progression 180–360 days postinfection was substantial (pooled incidences 19–24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27–1.18]), although results were highly variable between studies. Conclusions RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.

Currently, more than 3000 patients in the Netherlands receive long-term ventilatory support. In the majority of patients, long-term ventilatory support leads to increased survival without any complications. Diaphragm pacing with an external pacemaker (diaphragm pacing system, DPS) seems an attractive alternative for long-term ventilatory support by mask or tracheostomy. Scientific research has since shown that DPS is effective in patients with high cervical paraplegia. In addition, patients with congenital central hypoventilation syndrome are also eligible for DPS. Patients with diaphragm paralysis are a new group of patients who may be eligible for DPS. Two European studies have shown that DPS should not be used in patients with amyotrophic lateral sclerosis. In our experience, patients are no longer completely dependent on a ventilator or may even be able to discontinue using one if the procedure was successful. In the Netherlands, as far as we know, the technique is only used at the University Medical Center Groningen.

Quality-of-life (QOL) in patients with respiratory illness is a topic of increasing interest to clinicians and researchers. In a multicentre trial, which studies the long-term effects of three medication regimens (beta-agonist plus either placebo, anticholinergic agent or corticosteroid, all by inhalation) in patients with chronic nonspecific lung disease ((CNSLD): asthma and chronic obstructive pulmonary disease (COPD)), quality-of-life was included as an additional outcome measure. We wanted to provide a baseline assessment of quality-of-life in 274 adult patients with a mild to moderate degree of CNSLD. Quality-of-life was measured using a set of six standardized tests: Anxiety, Depression and Sleep Disorders, Optimism and Stigma, and Activities of Daily Living were assessed via scales with adequate validity and reliability, as established in previous work in Dutch patients with CNSLD. We found that quality-of-life was mildly impaired in these patients. Although differences with a reference group were present throughout, these were not significant, probably due to selection of relatively young, clinically stable, and highly motivated patients for our study. Quality-of-life scores showed higher correlation coefficients (0.20 < r < 0.38) to symptom scores than did results of pulmonary function tests (r < 0.015). In logistic regression models, absence from work and hospitalizations due to CNSLD were partly determined by quality-of-life scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of exacerbation frequency plays an increasingly important role in interventions in chronic obstructive pulmonary disease (COPD). To reduce this frequency efficiently, patients at risk for frequent exacerbations need to be identified.The objective of the study was to identify predictors for frequent exacerbations from multiple domains of COPD during a stable phase of the disease. Data of multiple domains of COPD were collected from 121 patients with moderate to severe COPD. Patients were divided into infrequent (2 exacerbations per year) and frequent (≥2 exacerbations) exacerbators.St. George's Respiratory Questionnaire (SGRQ) total score and a course of oral corticosteroid within 3 months prior to the study together predicted best whether patients would be infrequent or frequent exacerbators over the course of the next year. Each unit increase in total SGRQ score was associated with a 3% higher risk of being a frequent exacerbator [odds ratio (OR) = 1.03; 95% confidence interval (CI): 1.00-1.06; P = 0.047]. Patients who received a course of oral corticosteroids in the period of 3 months prior to the study had a three-fold increased risk of being a frequent exacerbator (OR = 3.17; 95% CI: 1.20-8.34; P = 0.02). Furthermore, we observed that a sizable number of patients switched from being a frequent to an infrequent exacerbator and vice versa.Health-related quality of life and a course of oral corticosteroid in the past 3 months are the best predictors of future exacerbator status. The predictive value of the model is, however, still insufficient. Furthermore, our data suggest, in contrast to previous observations, that exacerbation frequency is not a constant feature.

Bronchiectasis is usually a complication of previous lower respiratory infection, and causes chronic cough and copious production of sputum, which is often purulent. Bronchiectasis may cause signs of chronic obstructive pulmonary disease. It can also be associated with cystic fibrosis and other congenital disorders, foreign body inhalation, and other causes of lung damage.We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with bronchiectasis but without cystic fibrosis? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We performed a GRADE evaluation of the quality of evidence for interventions.We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria.In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergic therapy, bronchopulmonary hygiene physical therapy, exercise or physical training, hyperosmolar agents (inhaled), leukotriene receptor antagonists, methyl-xanthines (oral), mucolytics (bromhexine or deoxyribonuclease), prolonged-use antibiotics, beta(2) agonists, steroids (inhaled, oral), and surgery.

There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response.We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients.One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 microg/day b.i.d. or fluticasone propionate 250 microg/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double-blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% fall in FEV1 (PC20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response.We found that changes in FEV1, PC20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV1, but not for change in PC20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (or = 3%) correctly predicted an improvement in PC20 Mch in only 65% of the patients.Our findings show that baseline values of the clinical parameters used as outcome parameters are the major predictors of clinical response to corticosteroids. Eosinophil percentage in blood or sputum adds to this, whereas ECP provides no additional information. Correct prediction of clinical response in an individual patient, however, remains poor with our currently used clinical and inflammatory parameters.

Background: The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful. Phase 1: In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a beta(2)-agonist plus inhaled corticosteroid (BA+CS) was more effective in improving the FEV(1) and the provocative concentration of histamine causing a 20% reduction in FEV(1) (PC20) than treatment with a beta(2)-agonist plus anticholinergic (BA+AC) or placebo (BA+PL). Phase 2: We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 mu g beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA+/-AC) could also improve FEV(1) and PC20 to the same degree, A distinction was made between patients with predominantly asthma (high baseline reversibility, Delta FEV(1) greater than or equal to 9% of predicted), and predominantly COPD (low baseline reversibility, Delta FEV(1) Results: Improvement of FEV(1) percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p=0.13) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively), PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p=0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p=0.19). Conclusions: Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV(1), improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Airways hyperresponsiveness is a hallmark of asthma, and many patients with COPD also demonstrate hyperresponsiveness. Inhaled corticosteroids improve hyperresponsiveness, but the extent of improvement may vary considerably between patients. This study was designed to determine which patient characteristics predict these differences in response. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if PC20 less than or equal to 8 mg/ml and FEV(1)

Background - Despite effective treatments, the morbidity and mortality of obstructive airways disease (asthma and COPD) remains high. Home monitoring of peak expiratory dow (PEF) is increasingly being advocated as an aid to better management of obstructive airways disease. The few available studies describing effects of treatment on the level and variation of PEF have involved relatively small numbers of subjects and did not use control groups. Methods - Patients aged 18-60 years were selected with PC20 less than or equal to 8 mg/ml and FEV(1) Results - Improvements in PEF occurred within the first three months of treatment with BA + CS and was subsequently maintained: the mean (SE) increase in morning PEF was 51 (8) l/min in the BA + CS group compared with no change in the other two groups. Similarly, afternoon PEF increased by 22 (7) l/min. Diurnal variation in PEF (amplitude %mean) decreased from 18.0% to 10.2% in the first three months of treatment with BA + CS. Within-subject relations between changes in diurnal variation in PEF and changes in PC20 were found to be predominantly negative (median rho-0.40) but with a large scatter. Relations between diurnal variation ation in PEF and changes in symptom scores, FEV(1), and bronchodilator response were even weaker. Conclusions - In patients with moderately severe obstructive airways disease, PEF rates and variation are greatly improved by inhaled corticosteroids. Since the relation of diurnal PEF variation with PC20 symptoms, FEV(1), and bronchodilator response were all weak, these markers of disease severity may all provide different information on the actual disease state. PEF measurements should be used in addition to the other markers but not instead of them.

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) < or = 8 mg.ml-1, and forced expiratory volume in one second (FEV1) < 95% confidence intervals (CI) of predicted normal. The independent influences of baseline PC20FEV1, inspiratory vital capacity (IVC), bronchodilator response, smoking habits, and allergy both on the "immediate" (within 3 months) response in FEV1 and the change in long-term (from 3 months onwards) slope of FEV1 with inhaled corticosteroids were analysed. Patients had a larger "immediate" improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of "immediate" response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking. In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.

Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bron-chitis, and 36 could not be classified. Their mean (SD) FEV % pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV % pred (p