BMI predicts exercise induced bronchoconstriction in asthmatic boys

Background

Exercise induced bronchoconstriction (EIB) is a frustrating morbidity of asthma in children. Obesity has been associated with asthma and with more severe EIB in asthmatic children.

Objectives

To quantify the effect of BMI on the risk of the occurrence of EIB in children with asthma.

Methods

Data were collected from six studies in which exercise challenge tests were performed according to international guidelines. We included 212 Children aged 7‐18 years, with a pediatrician‐diagnosed mild‐to‐moderate asthma.

Results

A total of 103 of 212 children (49%) had a positive exercise challenge (fall of FEV₁ ≥ 13%). The severity of EIB, as measured by the maximum fall in FEV₁, was significantly greater in overweight and obese children compared to normal weight children (respectively 23.9% vs 17.9%; P = 0.045). Asthmatic children with a BMI z‐score around +1 had a 2.9‐fold higher risk of the prevalence of EIB compared to children with a BMI z‐score around the mean (OR 2.9; 95%CI: 1.3‐6.1; P < 0.01). An increase in BMI z‐score of 0.1 in boys led to a 1.4‐fold increased risk of EIB (OR 1.4; 95%CI: 1.0‐1.9; P = 0.03). A reduction in pre‐exercise FEV₁ was associated with a higher risk of EIB (last quartile six times higher risk compared to highest quartile (OR 6.1 [95%CI 2.5‐14.5]).

Conclusions

The severity of EIB is significantly greater in children with overweight and obesity compared to non‐overweight asthmatic children. Furthermore, this study shows that the BMI‐z‐score, even with a normal weight, is strongly associated with the incidence of EIB in asthmatic boys.

     

Ethnic differences in spirometry measurements in China: Results from a large community‐based epidemiological study

Background and objective

No previous studies have examined differences in spirometry measurements among ethnic populations in China, and factors which may influence ethnic differences are unclear. Our study aimed to investigate whether forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) differ among Han Chinese and other ethnic minorities in China.

Methods

We recruited 7137 individuals aged 35–70 years from four areas of China inhabited by ethnic minority groups between 2007 and 2009. We conducted spirometry tests for all available participants, and compared FEV₁ and FVC among Uygur, Hui, Mongolian, Dai and Han Chinese ethnicities, using nonlinear multiplicative regression models.

Results

A total of 2005 healthy never‐smokers were enrolled in the analysis. For all ethnicities, spirometry values increased with height and decreased with age; FEV₁ and FVC were consistently higher in males than in females. Compared with Han Chinese, FEV₁ was 4.42% (95% CI: 2.11–6.78%) higher in Mongolians, 4.08% (95% CI: 1.33–6.76%) lower in Uygurs, 4.39% (95% CI: 1.33–7.35%) lower in Hui people and 4.72% (95% CI: 1.80–7.55%) lower in Dai people, after adjusted for potential confounders including height, age, sex and place of residence. We observed similar differences for FVC.

Conclusions

We detected significant differences in spirometry measurements among ethnic populations in China. Such differences cannot be fully explained by demographic, anthropometric or socioeconomic factors, but may also be attributed to genetic background as well as indoor and outdoor environmental exposures that need further investigation.

     

Nasal high flow therapy and PtCO2 in stable COPD: A randomized controlled cross‐over trial

Background and objective

Hypercapnia is associated with worse clinical outcomes in exacerbations of COPD. The present study aimed to determine the effects of nasal high flow (NHF) therapy on transcutaneous partial pressure of carbon dioxide (PtCO₂) in stable COPD patients.

Methods

In a single‐blind randomized controlled cross‐over trial, 48 participants with COPD were allocated in random order to all of four 20 min interventions: NHF at 15 L/min, 30 L/min and 45 L/min or breathing room air with each intervention followed by a washout period of 15 min. The primary outcome measure was PtCO₂ at 20 min, adjusted for baseline PtCO₂. Secondary outcomes included respiratory rate at 20 min, adjusted for baseline.

Results

The mean (95% CI) change in PtCO₂ at 20 min was −0.6 mm Hg (−1.1 to 0.0), P = 0.06; −1.3 mm Hg (−1.9 to 0.8), P < 0.001; and −2.4 mm Hg (−2.9 to −1.8), P < 0.001; for NHF at 15 L/min, 30 L/min and 45 L/min compared with room air, respectively. The mean (95% CI) change in respiratory rate at 20 min was −1.5 (−2.7 to −0.3), P = 0.02; −4.1 (−5.3 to −2.9), P < 0.001; and −4.3 (−5.5 to −3.1), P < 0.001; breaths per minute compared with room air, respectively.

Conclusion

NHF results in a small flow‐dependent reduction in PtCO₂ and respiratory rate in patients with stable COPD.

     

Oesophageal diameter is associated with severity but not progression of systemic sclerosis‐associated interstitial lung disease

Background and objective

It is unknown whether oesophageal disease is associated with systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) severity, progression or mortality.

Methods

High‐resolution computed tomography (HRCT) scans from 145 SSc‐ILD patients were scored for fibrosis score, oesophageal diameter and presence of hiatal hernia. Fibrosis asymmetry was calculated as: (most affected side − least affected side)/(most affected side + least affected side). Mixed effects models were used for repeated measures analyses.

Results

Mean fibrosis score was 8.6%, and most patients had mild‐to‐moderate physiological impairment. Every 1 cm increase in oesophageal diameter was associated with 1.8% higher fibrosis score and 5.5% lower forced vital capacity (FVC; P ≤ 0.001 for unadjusted and adjusted analyses). Patients with hiatal hernia had 3.9% higher fibrosis score, with persistent differences on adjusted analysis (P = 0.001). Oesophageal diameter predicted worsening fibrosis score over the subsequent year (P = 0.02), but not when adjusting for baseline fibrosis score (P = 0.16). Oesophageal diameter was independently associated with mortality (P = 0.001). Oesophageal diameter was not associated with asymmetric disease or radiological features of gross aspiration.

Conclusion

Oesophageal diameter and hiatal hernia are independently associated with SSc‐ILD severity and mortality, but not with ILD progression or asymmetric disease. Oesophageal disease is unlikely to be a significant driver of ILD progression in SSc.

     

Comparison of respiratory system impedance in asthma and COPD: A prospective observational study

Background and objective

A single assessment of within‐breath variations of respiratory system reactance (Xrs) at 5 Hz (ΔX5) measured by the forced oscillation technique (FOT) has been reported to be useful for the detection of pathophysiological changes in chronic obstructive pulmonary disease (COPD) and asthma. We examined longitudinal changes in respiratory system resistance (Rrs) and Xrs during tidal breathing between stable asthma and COPD patients in order to clarify the features of changes of respiratory system impedance and airflow limitation for these conditions.

Methods

Between April 2013 and September 2013, outpatients with a COPD or asthma diagnosis were recruited. We examined forced expiratory volume in 1 s (FEV₁) and FOT every 6 months until September 2015. Annual changes were estimated from the linear regression curve slope.

Results

We included 57 and 93 subjects with COPD and asthma, respectively. The median follow‐up period was 26 months (range: 24–29 months). Within‐breath analysis showed that the difference between mean Rrs at 5 Hz and 20 Hz was significantly lower, and ΔX5 more negative, in COPD than in asthma patients. With regard to annual changes, only ΔX5 was significantly different, more negative, in COPD than in asthma patients. Comparing between COPD subjects of Global Initiative Chronic Obstructive Lung Disease (GOLD) stage I/II and those with asthma, there were no significant differences in respiratory system impedance at enrolment, while annual change in ΔX5 was significantly more negative in mild COPD than in asthma patients.

Conclusion

ΔX5 may be useful for long‐term assessment of airflow limitation in COPD.

     

Predictors of repeated acute hospital attendance for asthma in children: A systematic review and meta‐analysis

Background

Asthma attacks are common and have significant physical, psychological, and financial consequences. Improving the assessment of a child's risk of subsequent asthma attacks could support front‐line clinicians’ decisions on augmenting chronic treatment or specialist referral. We aimed to identify predictors for emergency department (ED) or hospital readmission for asthma from the published literature.

Methods

We searched MEDLINE, EMBASE, AMED, PsycINFO, and CINAHL with no language, location, or time restrictions. We retrieved observational studies and randomized controlled trials (RCT) assessing factors (personal and family history, and biomarkers) associated with the risk of ED re‐attendance or hospital readmission for acute childhood asthma.

Results

Three RCTs and 33 observational studies were included, 31 from Anglophone countries and none from Asia or Africa. There was an unclear or high risk of bias in 14 of the studies, including 2 of the RCTs. Previous history of emergency or hospital admissions for asthma, younger age, African‐American ethnicity, and low socioeconomic status increased risk of subsequent ED and hospital readmissions for acute asthma. Female sex and concomitant allergic diseases also predicted hospital readmission.

Conclusion

Despite the global importance of this issue, there are relatively few high quality studies or studies from outside North America. Factors other than symptoms are associated with the risk of emergency re‐attendance for acute asthma among children. Further research is required to better quantify the risk of future attacks and to assess the role of commonly used biomarkers.

     

Disease burden of mild asthma in China

Background and objective

The impact, treatment patterns and control of mild asthma are poorly understood for Chinese patients. This study describes the characteristics, therapeutic interventions and burden of mild asthma on patients residing in major cities of China.

Methods

The Respiratory Disease Specific Program 2015, a cross‐sectional survey, was conducted with Chinese physicians and their patients. The survey assessed clinical characteristics, asthma symptoms, exacerbations, rescue inhaler usage, treatment adherence, asthma control, work and activity impairments and healthcare utilization for patients prescribed Global Initiative for Asthma (GINA) Step 1 or 2 treatment defined mild asthma.

Results

From a total sample of 988 patients, 229 patients met the criteria for mild asthma, with 25.3% classified as Step 1 and 74.7% as Step 2. Overall, 12.6% of patients were considered of high adherence to prescribed treatment. Physicians reported that 75% of patients overall were well controlled, although well‐controlled asthma as defined by GINA was achieved in only 14.2% of patients. 26.5% of patients indicated daily use of as‐needed rescue medication in the last 4 weeks. 17.8% of patients experienced ≥1 exacerbations in the last 12 months and impaired work productivity was 27.2% overall.

Conclusion

Less than 15% of patients were well controlled according to GINA criteria despite physicians reporting the majority of patients were well controlled. Over one‐fourth of patients relied on daily rescue inhaler medication, while exacerbation frequency and work and activity impairment were higher than might reasonably be expected in a mild asthmatic population.

     

Role of sublingual immunotherapy in the treatment of asthma: An updated systematic review

Background

The purpose of the systematic review is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of allergic asthma.

Methods

PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health‐care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome.

Results

Fourteen RCTs (n = 2585) assessed the efficacy of SLIT for asthma. The RCTs utilized house dust mite (HDM), birch, or grass allergen. SLIT improved asthma symptoms (high SOE), decreased use of long‐term control medication, and improved forced expiratory volume in 1 second (FEV₁) (moderate SOE). SLIT may decrease quick‐relief medication use, and improve disease‐specific quality of life (low SOE). For safety, 20 RCTs and 10 observational studies (n = 3621) were identified. Local (risk differences ranged from ?0.03 to +0.765) and systemic allergic reactions (risk differences ranged from ?0.03 to +0.06) were a common occurrence in SLIT and control groups. Life‐threatening reactions were uncommon, with 3 cases of anaphylaxis and no deaths reported.

Conclusion

There is moderate‐to‐high strength evidence that SLIT improves allergic asthma symptoms, reduces long‐term control medication use, and improves FEV₁ based on studies of HDM, birch, and grass. SLIT rarely is associated with life‐threatening adverse events.

     

Defining ‘healthy’ in preschool‐aged children for forced oscillation technique reference equations

Background and objective

Selecting ‘healthy’ preschool‐aged children for reference ranges may not be straightforward. Relaxing inclusion criteria for normative data does not affect spirometry z‐scores. We therefore investigated the effect of similarly relaxing inclusion criteria in preschoolers on reference ranges for respiratory impedance (Zrs) using a modified forced oscillation technique (FOT).

Methods

The International Study of Asthma and Allergies in Childhood questionnaire classified 585 children into a healthy and five mutually exclusive groups. Zrs was measured between 4 and 26 Hz and resistance (R) and compliance (C) obtained by model fitting. Prediction models were determined using mixed effect models and z‐scores compared between healthy children and the five groups.

Results

Zrs data were obtained for 494 participants (4.30 ± 0.7 years) on 587 occasions. Comparison of the Zrs z‐scores between the healthy children and the health groups found significant differences in children with asthma, current wheeze and respiratory symptoms, but not in children born preterm or with early‐life wheeze. Adding these two groups to the healthy dataset had no significant effect on the distribution of z‐scores and increased the size of the dataset by 22.3%.

Conclusion

Our data suggest that preschool‐aged children born preterm or with early‐life wheeze can be included in FOT reference equations, while those with asthma, current wheeze and respiratory symptoms within 4 weeks of testing should be excluded. This more inclusive approach results in more robust FOT reference ranges.

     

Vitamin D and respiratory health in the Busselton Healthy Ageing Study

Background and objective

The relationship between vitamin D and respiratory disease was examined by cross‐sectional analysis of a large community‐based sample.

Methods

Serum 25‐hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45–69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C).

Results

Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50–100 nmol/L group in Model C).

Conclusion

Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.

     

Alcohol‐induced respiratory symptoms improve after aspirin desensitization in patients with aspirin‐exacerbated respiratory disease

Background

Aspirin‐exacerbated respiratory disease (AERD) is characterized by chronic eosinophilic rhinosinusitis, nasal polyps, asthma, and respiratory sensitivity to aspirin and nonsteroidal anti‐inflammatory drugs (NSAIDs). In addition to sensitivity to aspirin and NSAIDs, the majority of patients with AERD have been reported to have respiratory intolerance associated with the consumption of alcohol.

Methods

A multicenter prospective cohort study was performed. Patients with AERD confirmed by aspirin challenge were eligible to participate. Those who described themselves as able to tolerate alcohol consumption were excluded. Patients underwent aspirin desensitization following endoscopic sinus surgery. A questionnaire was distributed to patients before and after desensitization to determine pre‐desensitization and post‐desensitization symptoms associated with alcohol ingestion.

Results

Forty‐five patients were enrolled and 37 patients completed the study. The most common pre‐desensitization symptoms were nasal congestion (95.6%), rhinorrhea (46.7%), and wheezing (40%). Improvement in the ability to tolerate alcohol was noted in 86.5% of participants (95% confidence interval [CI], 75.5% to 97.5%) and 70.3% of participants (95% CI, 55.5% to 85.0%) described desensitization to be “very helpful” or “extremely helpful” for their ability to tolerate alcohol.

Conclusion

The majority of patients with AERD who experience respiratory symptoms with alcohol consumption describe improvement in this domain following aspirin desensitization.

     

Mortality in patients with community‐onset pneumonia at low risk of drug‐resistant pathogens: Impact of β‐lactam plus macrolide combination therapy

Background and objective

Drug‐resistant pathogen (DRP) risk stratification is important for choosing a treatment strategy for community‐onset pneumonia. Evidence for benefits of non‐antipseudomonal β‐lactam plus macrolide combination therapy (BLM) on mortality is limited in patients at low DRP risk. Risk factors for mortality remain to be clarified.

Methods

Post hoc analysis using a prospective multicentre study cohort of community‐onset pneumonia was performed to assess 30‐day differences in mortality between non‐antipseudomonal β‐lactam monotherapy (BL) and BLM groups. Logistic regression analysis was performed to assess the therapeutic effect and risk factors for mortality in patients at low DRP risk.

Results

In total, 594 patients with community‐onset pneumonia at low DRP risk (369 BL and 225 BLM) were analysed. The 30‐day mortality in BL and BLM was 13.8% and 1.8%, respectively (P < 0.001). Multivariate analysis showed that BLM reduced the 30‐day mortality (adjusted odds ratio: 0.28, 95% CI: 0.09–0.87) compared with BL. Independent prognostic factors for 30‐day mortality included arterial partial pressure of carbon dioxide (PaCO₂) > 50 mm Hg, white blood cell count < 4000/mm³, non‐ambulatory status, albumin < 3.0 g/dL, haematocrit < 30%, age ≥ 80 years, respiratory rate > 25/min and body temperature < 36°C.

Conclusion

In patients with community‐onset pneumonia at low DRP risk, BLM treatment reduced 30‐day mortality compared with BL. Independent risk factors for mortality are potential confounding factors when assessing antibiotic effects in randomized clinical trials.

     

Regression equations to estimate the 2‐min walk distance in an adult Asian population aged 40–75 years

Background and objective

There is increased use of the 2‐min walk test (2MWT) to assess functional exercise capacity. However, the distance achieved during this test may be difficult to interpret in the absence of reference values from a local population. Regression equations to estimate the 2‐min walk distance (2MWD) only exist for American and Brazilian populations. The objective of this study was to develop regression equations to estimate the 2MWD in Malaysian adults who were free from major health problems.

Methods

Eighty‐seven adults (43 males; mean ± SD age: 57.1 ± 9.6 years) performed two 2MWT using a standardized protocol. Heart rate (HR) was recorded every 30 s during the test. Stepwise multiple regression analysis was performed using age, gender, height, weight and change in HR (ΔHR) as independent variables, and better of the two 2MWD as the dependent variable. A second regression equation, without ΔHR, was planned if ΔHR was retained as one of the predictors of the 2MWD in the first equation.

Results

The better of the two 2MWD was 200 ± 34 m. Males walked 33 ± 6 m further than females (P < 0.001). The two regression equations were 196 − 1.1 × age, years + 1.0 × ΔHR, bpm + 31.2 × gender (R² = 0.73) and 279 − 1.7 × age, years + 35.9 × gender (R² = 0.47) with females = 0 and males = 1.

Conclusion

The equations derived in this study may facilitate the interpretation of the 2MWD in clinical populations in Malaysia, as well as in countries with similar cultural backgrounds to Malaysia.

     

Asthma onset pattern and patient outcomes in a chronic rhinosinusitis population

Background

Chronic rhinosinusitis (CRS) is strongly associated with comorbid asthma. This study compares early‐onset and late‐onset asthma in a CRS population using patient‐reported and clinical characteristics.

Methods

At enrollment into a clinical registry, CRS patients completed the 22‐item Sino‐Nasal Outcome Test (SNOT‐22), Asthma Control Test (ACT), mini‐Asthma Quality of Life Questionnaire (miniAQLQ), the 29‐item Patient‐Reported Outcomes Measurement Information System (PROMIS‐29), and medication use questionnaires. Patients also reported comorbid asthma and age at first asthma diagnosis. Early‐onset (<18 years) and late‐onset (>18 years) asthma groups were defined. Analysis of variance (ANOVA), chi‐square, and Kruskal‐Wallis tests were used to compare patient responses.

Results

A total of 199 non‐asthmatic (56.1%), 71 early‐onset asthmatic (20.0%), and 85 late‐onset asthmatic (23.9%) CRS patients completed the survey. Body mass index (BMI) was significantly higher in late‐onset asthmatic (p = 0.046) while age, gender, race, and smoking history did not differ with time of asthma onset. SNOT‐22, ACT, and miniAQLQ were not different between asthma groups, but late‐onset asthmatics had significantly lower physical function than non‐asthmatics (p = 0.008). Compared to non‐asthmatics, late‐onset asthmatics showed increased rates of nasal polyps (p < 0.001), higher Lund‐Mackay scores (p = 0.005), and had received more oral steroid courses (p < 0.001) and endoscopic surgeries (p = 0.008) for CRS management. Late‐onset asthmatics compared to early‐onset asthmatics showed increased nasal polyposis (p = 0.011) and oral steroid courses for CRS (p = 0.003).

Conclusion

While CRS‐specific and asthma‐specific patient‐reported outcome measures (PROMs) were not significantly different among groups, CRS patients with late‐onset asthma had poorer physical function, more frequent nasal polyposis, and required increased treatment for CRS. Late‐onset asthma may predict more severe disease in CRS.

     

Long‐term clinical results of bioresorbable absorb scaffolds using the PSP‐technique in patients with and without diabetes

Objectives

We evaluated clinical results up to 36 months after implantation of Absorb BVS using PSP‐technique and compared the outcome of patients with and without diabetes mellitus.

Background

Absorb II demonstrated that interventional treatment of coronary artery disease with bioresorbable vascular scaffolds (BVS) without proper PSP‐technique (pre‐dilation, proper sizing, and post‐dilation) is associated with an increased thrombotic risk, even in simple lesions.

Methods

In this prospective study 319 patients with 420 lesions were enrolled and treated with the Absorb BVS. Pre‐dilation was mandatory and post‐dilation with a high‐pressure balloon was performed in patients with a scaffold length >12 mm. Patients were clinically followed up to 3 years. Primary outcome measure was the device‐oriented endpoint (DoCE) defined as cardiac death, myocardial infarction not clearly related to a non‐target vessel and target lesion revascularization.

Results

DoCE was 5.0%, 7.1%, and 10.0% after 12, 24, and 36 months for the total population. Rate of scaffold thrombosis was 0.5%, 0.8%, and 1.4% after 12, 24, and 36 months. Rate of DoCE was higher in the diabetic subgroup with 9.1%, 12.6%, and 12.9% after 12, 24, and 36 months compared with 4.0% (P = 0.13), 5.6% (P = 0.05), and 9.9% (P = 0.20) in patients without diabetes mellitus.

Conclusions

Patients treated with the Absorb BVS using the PSP‐technique show good results up to 3 years with a low rate of scaffold thrombosis. Patients suffering from diabetes mellitus have an increased rate of DoCE compared with non‐diabetic patients.

Clinical Trial Registration

clinicaltrials.gov_NCT02162056 .

     

Surfactant protein D multimerization and gene polymorphism in COPD and asthma

Background and objective

A structural single nucleotide polymorphism rs721917 in the surfactant protein D (SP‐D) gene, known as Met11Thr, was reported to influence the circulating levels and degree of multimerization of SP‐D and was associated with both COPD and atopy in asthma. Moreover, disease‐related processes are known to degrade multimerized SP‐D, however, the degree of the protein degradation in these diseases is not clarified. We aimed to determine the distribution of multimerized (high molecular weight (HMW)) and non‐multimerized (low molecular weight (LMW)) species of serum SP‐D and their correlation with genetic polymorphisms and presence of disease in Lebanese COPD and asthmatic patients.

Methods

Serum SP‐D levels were measured by ELISA in 88 COPD, 121 asthmatic patients and 223 controls. Randomly selected subjects were chosen for genotyping of rs721917 and multimerization studies. HMW and LMW SP‐D were separated by gel permeation chromatography.

Results

Serum SP‐D levels were significantly increased in patients with COPD, but not in asthmatic patients, when compared to controls. Met11Thr variation strongly affected serum SP‐D levels and the degree of multimerization, but was not associated with COPD and asthma in the study. Remarkably, HMW/LMW serum SP‐D ratio was significantly lower in Met11/Met11 COPD and asthmatic patients compared to controls.

Conclusion

Collectively, non‐multimerized species of serum SP‐D were dominant in COPD and asthmatic patients suggesting that degradation of SP‐D takes place to a significant degree in pulmonary disease. Assays that can separate SP‐D proteolytic breakdown products or modified forms from naturally occurring SP‐D trimers may result in optimal disease markers for pulmonary inflammatory diseases.

     

Predictors for long‐term survival after transcatheter edge‐to‐edge mitral valve repair

Objectives

To determine predictors for long‐term outcome in high‐risk patients undergoing transcatheter edge‐to‐edge mitral valve repair (TMVR) for severe mitral regurgitation (MR).

Background

There is no data on predictors of long‐term outcome in high‐risk real‐world patients.

Methods

From August 2009 to April 2011, 126 high‐risk patients deemed inoperable were treated with TMVR in two high‐volume university centers.

Results

MR could be successfully reduced to grade ≤2 in 92.1% of patients (116/126 patients). Long‐term clinical follow‐up up to 5 years (95.2% follow‐up rate) revealed a mortality rate of 35.7% (45/126 patients). Repeat mitral valve treatment (surgery or intervention) was needed in 19 patients (15.1%). Long‐term clinical improvement was demonstrated with 69% of patients being in NYHA class ≤II. In a multivariable Cox regression analysis, the post‐procedural grade of MR (hazard ratio [HR] 1.55 per grade, P = 0.035), the left ventricular ejection fraction (HR 0.58 for difference between 75th and 25th percentile, P = 0.031) and the glomerular filtration rate (HR 0.33 for 75th vs 25th percentile, P < 0.001) were independent predictors for long‐term mortality. Patients with primary MR and a post‐procedural MR grade ≤1 had the most favorable long‐term outcome.

Conclusions

This study determines predictors of long‐term clinical outcome after TMVR and demonstrates that the grade of residual MR determines long‐term survival. Our data suggest that it might be of benefit reducing residual MR to the lowest possible MR grade using TMVR—especially in selected high‐risk patients with primary MR who are not considered as candidates for surgical MVR.

     

Early increase of VEGF‐A is associated with resolution of ventilator‐associated pneumonia: Clinical and experimental evidence

Background and objective

The role of vascular endothelial growth factor (VEGF)‐A in the resolution of ventilator‐associated pneumonia (VAP) was investigated in clinical and mouse pneumonia models.

Methods

VEGF‐A was measured for seven consecutive days by an immunosorbent assay in sera of 82 patients with VAP and changes from baseline were correlated with the resolution of VAP. Experimental animals were challenged intratracheally with Pseudomonas aeruginosa . Mouse bronchoalveolar lavage (BAL) samples and segments of lung tissue were obtained at 24, 48 and 124 h after bacterial challenge. Levels of VEGF‐A, tumour Necrosis Factor alpha (TNF‐α), interleukin (IL)‐1β, interferon‐gamma (IFNγ) and myeloperoxidase (MPO) activity were measured in these samples.

Results

VAP resolved in 36.1% of patients with a less than 45% increase of VEGF‐A on day 5 compared to 65.2% of patients with a more than 45% increase (P = 0.014). This was also accompanied by an earlier resolution of VAP (log‐rank: 7.99; P = 0.005) and it was not pathogen‐specific. The increase of VEGF‐A was an independent variable associated with VAP resolution in forward logistic regression analysis where Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were included as independent variables. VEGF‐A in mouse BAL and lung tissue increased significantly at 124 h but not with the other mediators. In mice pre‐treated with bevacizumab, VEGF‐A concentrations decreased while TNF‐α and MPO significantly increased.

Conclusion

In patients, an association between increased levels of circulating VEGF‐A and VAP resolution was observed. The mouse study suggests that elevated VEGF‐A levels may be associated with lung inflammation resolution. Clinical trial registration: NCT00297674 at www.clinicaltrials.gov

     

Anesthetic ointment only (lidocaine/prilocaine) instead of injectable local lidocaine in trans‐radial catheterization: A viable no‐needle alternative

Objective

The aim of the present study was to assess the level of access site pain in patients undergoing transradial coronary catheterization by using topical application of an anesthetic ointment (lidocaine/prilocaine—AO) compared to standard local anesthesia (LA) by means of injectable lidocaine.

Methods

We prospectively studied 444 patients undergoing elective trans‐radial coronary angiography. The quality of analgesia was assessed using a visual analogue scale (VAS) immediately after the puncture and 30 min after the removal of the sheath. The number and duration of attempts before successful sheath insertion, as well as artery spasm, were compared between the two groups.

Results

Pain levels measured by VAS were found to be similar between the two groups during sheath insertion (VAS: AO: 4.84 ± 1.0 vs 4.82 ± 1.2, P = NS), as well as 30 min after sheath removal (VAS: AO: 0.07 ± 0.5 vs LA: 0.15 ± 0.6, P = NS). The time to obtain radial access was also not affected by the use of anesthetic ointment (AO: 62.24 ± 25.7 s vs LA: 64.04 ± 18.78 sec, P = NS). The rate of clinical or angiographic radial artery spasm was similar (8‐10%) between the groups (P = NS)

Conclusion

Use of a local anesthetic ointment, versus injectable lidocaine, in trans‐radial cardiac catheterization as means of local anesthesia, was found to be equally effective in terms of pain, artery spasm, or artery cannulation speed.

     

Radiographic fibrosis score predicts survival in systemic sclerosis‐associated interstitial lung disease

Background and objective

Interstitial lung disease (ILD ) is a common pulmonary manifestation of systemic sclerosis (SSc ). It is unknown whether radiographic fibrosis score predicts mortality in SSc ‐associated ILD (SSc‐ILD ). We retrospectively analysed patients with SSc‐ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality.

Methods

We identified SSc‐ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high‐resolution computed tomography (HRCT ) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model.

Results

The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT . The median follow‐up period was 56.6 months, and over the follow‐up period 15 patients died. The 5‐year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not.

Conclusion

A high radiographic fibrosis score was a poor prognostic factor in SSc‐ILD . More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern.