Hospitalised patients with coronavirus disease 2019 (COVID-19) as a result of SARS-CoV-2 infection have a high mortality rate and frequently require noninvasive respiratory support or invasive ...ventilation. Optimising and standardising management through evidence-based guidelines may improve quality of care and therefore patient outcomes.
A task force from the European Respiratory Society and endorsed by the Chinese Thoracic Society identified priority interventions (pharmacological and non-pharmacological) for the initial version of this "living guideline" using the PICO (population, intervention, comparator, outcome) format. The GRADE approach was used for assessing the quality of evidence and strength of recommendations. Systematic literature reviews were performed, and data pooled by meta-analysis where possible. Evidence tables were presented and evidence to decision frameworks were used to formulate recommendations.
Based on the available evidence at the time of guideline development (20 February, 2021), the panel makes a strong recommendation in favour of the use of systemic corticosteroids in patients requiring supplementary oxygen or ventilatory support, and for the use of anticoagulation in hospitalised patients. The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. The panel make strong recommendations against the use of hydroxychloroquine and lopinavir-ritonavir. Conditional recommendations are made against the use of azithromycin, hydroxychloroquine combined with azithromycin, colchicine, and remdesivir, in the latter case specifically in patients requiring invasive mechanical ventilation. No recommendation was made for remdesivir in patients requiring supplemental oxygen. Further recommendations for research are made.
The evidence base for management of COVID-19 now supports strong recommendations in favour and against specific interventions. These guidelines will be regularly updated as further evidence becomes available.
Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described.
To establish if ...there is a "frequent exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long-term clinical outcomes.
We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality.
A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval CI, 1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV
, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow-up. Mortality over up to 5 years of follow-up increased with increasing exacerbation frequency.
The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow-up.
Following discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 and subsequent elucidation of the varied CFTR protein abnormalities that result, a new era of cystic ...fibrosis management has emerged—one in which scientific principles translated from the bench to the bedside have enabled us to potentially treat the basic defect in the majority of children and adults with cystic fibrosis, with a resultant burgeoning adult cystic fibrosis population. However, the long-term effects of these therapies on the multiple manifestations of cystic fibrosis are still under investigation. Understanding the effects of modulators in populations excluded from clinical trials is also crucial. Furthermore, establishing appropriate disease measures to assess efficacy in the youngest potential trial participants and in those whose post-modulator lung function is in the typical range for people without chronic lung disease is essential for continued drug development. Finally, recognising that a health outcome gap has been created for some people and widened for others who are not eligible for, cannot tolerate, or do not have access to modulators is important.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pulmonary fibrosis is associated with significant morbidity. Data are scarce on the link between coronavirus disease (COVID-19) and pulmonary fibrosis. We aimed to assess the association between ...COVID-19 with pulmonary fibrosis.
We conducted a nested case-control study in a cohort of 2,894,801 adults without a diagnosis of pulmonary fibrosis. The underlying cohort consisted of members of the largest healthcare provider in Israel aged 18 years or older as of May 1, 2020. Subjects were followed up from cohort entry until June 30, 2022, for the occurrence of pulmonary fibrosis. Ten randomly selected controls were matched to each case of pulmonary fibrosis on age, sex, and calendar time. To account for surveillance bias a lag time of 60 days was used for ascertainment of prior COVID-19 and COVID-19 severity.
During follow-up 1284 patients were newly diagnosed with pulmonary fibrosis and matched with 12,840 controls. Multivariable conditional logistic-regression models showed that the odds ratio for pulmonary fibrosis was 1.80 (95% confidence interval, 1.47-2.19) in patients with COVID-19 compared with no COVID-19. The multivariable odds ratio for pulmonary fibrosis was 1.33 (1.06-1.68), 2.98 (1.16-7.65), and 9.30 (5.77-14.98) for mild, moderate, and severe COVID-19, respectively, compared with no COVID-19. The magnitude of the association was attenuated but remained statistically significant for severe disease when the lag time was extended to 180 days (1.08 0.78-1.49, 2.37 0.75-7.46, and 5.34 2.75-10.36 for mild, moderate, and severe COVID-19, respectively).
COVID-19 appears to be associated with an increased risk of pulmonary fibrosis and the magnitude of the association increases with COVID-19 severity.
•We report 3 cases of congenital cataracts in children exposed to ETI in utero.•In 2 of the cases, ETI components were detected in breast milk.•In all 3 cases known factors for congenital cataracts ...were not identified.•In all 3 cases cataracts were small and did not affect vision.•We suggest children exposed to ETI in utero are systematically tested for cataracts.
Elexacaftor-tezacaftor-ivacaftor (ETI) is known to pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of ivacaftor in rats demonstrated infant cataracts, but cataracts were not reported in human infants exposed to ivacaftor. We describe 3 cases of infants exposed to elexacaftor-tezacaftor-ivacaftor (ETI) in utero and while breast feeding who were found to have bilateral congenital cataracts within six months of birth. None of the infants had significant visual impairment from the cataracts nor any report of elevated liver function testing. These data highlight the need to counsel females who continue ETI throughout pregnancy and while breast feeding to consider cataract screen for their infants.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•We searched the ECFS-PR for inhaled antibiotic use in pwCF without PA infection.•30% of pwCF not chronically PA infected were treated with inhaled antibiotics.•The major determinant of inhaled ...antibiotic use is past chronic infection with PA.•Over follow up, no benefit has been seen for treatment with inhaled antibiotics.•Randomized trials of inhaled antibiotics in pwCF without PA infection are needed.
Long-term treatment with inhaled antibiotics is recommended for people with cystic fibrosis (pwCF) chronically infected with Pseudomonas aeruginosa (PA). However, pwCF without chronic PA infection are also commonly treated with inhaled antibiotics. Using data from the European Cystic Fibrosis Patient Registry (ECFSPR) we aimed to determine the prevalence and factors associated with inhaled antibiotic treatment in pwCF without chronic PA infection, and long-term outcomes with inhaled antibiotics use.
The ECFSPR was searched for pwCF 6 years of age and older who were not chronically infected with PA at baseline. Factors associated with inhaled antibiotic use were first assessed through a logistic regression. From this model a propensity score was computed for each individual, providing the likelihood of being treated with inhaled antibiotics. Long-term outcomes with and without inhaled antibiotics were assessed separately for propensity scores tertiles.
7210 pwCF without chronic PA infection at baseline were included, with 2722 (37.75%) receiving long-term treatment with inhaled antibiotics. Treatment with inhaled antibiotics was more prevalent with severe genotype, diabetes, pancreatic insufficiency, and past infection with chronic PA (OR 3.8, 95% CI, 2.88–5.04). Treatment with inhaled antibiotics was not associated with a reduced risk for acquisition of PA or other resistant pathogens, or with improved lung function decline, mortality, or transplantation.
Many pwCF without chronic PA infection are receiving long-term treatment with inhaled antibiotics despite lack of support from clinical trials or practice guidelines. We did not observe improve outcomes with inhaled antibiotics. Our findings suggest controlled studies evaluating specific inhaled antibiotic regimens targeting specific pathogens or indications be performed to determine their effect.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bronchiectasis is a heterogeneous, neglected disease with few multicentre studies exploring the causes, severity, microbiology, and treatment of the disease across Europe. This aim of this study was ...to describe the clinical characteristics of bronchiectasis and compare between different European countries.
EMBARC is an international clinical research network for bronchiectasis. We report on a multicentre, prospective, observational, non-interventional, cohort study (the EMBARC registry) conducted across 27 European countries and Israel. Comprehensive clinical data were collected from adult patients (aged ≥18 years) at baseline and annual follow-up visits using electronic case report form. Data from individual countries were grouped into four regions (the UK, northern and western Europe, southern Europe, and central and eastern Europe according to modified EU EuroVoc classification). Follow-up data were used to explore differences in exacerbation frequency between regions using a negative binomial regression model.
Between Jan 12, 2015, and April 12, 2022, 16 963 individuals were enrolled. Median age was 67 years (IQR 57–74), 10 335 (60·9%) participants were female and 6628 (39·1%) were male. The most common cause of bronchiectasis in all 16 963 participants was post-infective disease in 3600 (21·2%); 6466 individuals (38·1%) were classified as idiopathic. Individuals with bronchiectasis experienced a median of two exacerbations (IQR 1–4) per year and 4483 (26·4%) patients had a hospitalisation for exacerbation in the previous year. When examining the percentage of all isolated bacteria, marked differences in microbiology were seen between countries, with a higher frequency of Pseudomonas aeruginosa and lower Haemophilus influenzae frequency in southern Europe, compared with higher H influenzae in the UK and northern and western Europe. Compared with other regions, patients in central and eastern Europe had more severe bronchiectasis measured by the Bronchiectasis Severity Index (51·3% vs 35·1% in the overall cohort) and more exacerbations leading to hospitalisations (57·9% vs 26·4% in the overall cohort). Overall, patients in central and eastern Europe had an increased frequency of exacerbations (adjusted rate ratio RR 1·12, 95% CI 1·01–1·25) and a higher frequency of exacerbations leading to hospitalisations (adjusted RR 1·71, 1·44–2·02) compared with patients in other regions. Treatment of bronchiectasis was highly heterogeneous between regions.
Bronchiectasis shows important geographical variation in causes, microbiology, severity, and outcomes across Europe.
European Union–European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative.
For the Arabic, French, German, Greek, Hebrew, Irish, Russian and Spanish translations of the abstract see Supplementary Materials section.
Inhaled ultrafine particle (UFP) content in exhaled breath condensate (EBC) was observed as an airway inflammatory marker and an indicator of exposure to particulate matter (PM). The exceptional ...decline in air pollution during the COVID-19 lockdown was an opportunity to evaluate the effect of environmental changes on UFP airway content. We collected EBC samples from 30 healthy subjects during the first lockdown due to COVID-19 in Israel (March-April 2020) and compared them to EBC samples retrieved during April-June 2016 from 25 other healthy subjects (controls) living in the same northern Israeli district. All participants underwent EBC collection and blood sampling. Ambient air pollutant levels were collected from the Israeli Ministry of Environmental Protection's online database. Data were acquired from the monitoring station closest to each subject's home address, and means were calculated for a duration of 1 month preceding EBC collection. UFP contents were measured in the EBC and blood samples by means of the NanoSight LM20 system. There was a dramatic reduction in NO, NO
, SO
, and O
levels during lockdown compared to a similar period in 2016 (by 61%, 26%, 50%, and 45%, respectively). The specific NO
levels were 8.3 ppb for the lockdown group and 11.2 ppb for the controls (
= 0.01). The lockdown group had higher UFP concentrations in EBC and lower UFP concentrations in serum compared to controls (0.58 × 10
/mL and 4.3 × 10
/mL vs. 0.43 × 10
/mL and 6.7 × 10
/mL,
= 0.05 and
= 0.03, respectively). In this observational study, reduced levels of air pollution during the COVID-19 lockdown were reflected in increased levels of UFP airway contents. The suggested mechanism is that low airway inflammation levels during lockdown resulted in a decreased UFP translocation to serum. Further studies are needed to confirm this hypothesis.
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