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.

     

Potential pathogenicity of Inquilinus limosus in a pediatric patient with cystic fibrosis

Presentation

Patient is a 6‐year‐old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF.

Course

I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement.

Discussion

This case discusses the importance of a rare organism in the CF population. Targeting I. limosus was key to recovery, revealing its potential pathogenicity.

     

Children with severe acute asthma admitted to Dutch PICUs: A changing landscape

The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased.

Objectives

We investigated whether this trend in SAA PICU admissions is present in the Netherlands.

Methods

A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2‐18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality.

Results

In the 11‐year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P < 0.001) and fewer children needed invasive ventilation (P < 0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1 mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P = 0.005). The proportion of steroid‐naïve patients increased from 35% to 54% (P = 0.004), with a significant increase in both age groups (2‐4 years [P = 0.026] and 5‐17 years [P = 0.036]).

Conclusions

The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid‐naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals.

     

Serum soluble receptor for advanced glycation end‐products during acute bronchiolitis in infant: Prospective study in 93 cases

Introduction

Acute bronchiolitis is a major cause of acute respiratory distress in infants. The soluble receptor for advanced glycation end‐products (sRAGE) is a biomarker of pulmonary damage processes, with a diagnostic and a prognostic value in acute respiratory distress syndrome (ARDS). The RAGE pathway is also implicated in the pathogenesis of other respiratory diseases like asthma, but the value of sRAGE levels in acute bronchiolitis remains under‐investigated.

Material and methods

A prospective, observational, and analytical study was conducted at Clermont‐Ferrand University Hospital. The main objective was to evaluate the correlation between serum sRAGE and clinical severity of bronchiolitis in hospitalized infants aged <1 year. We analyzed correlations between serum sRAGE and Wainwright score, short‐term morbidity attributable to bronchiolitis, causal viruses and risk for recurrent wheezing at 1 year.

Results

The study included 93 infants. sRAGE levels were significantly lower in acute bronchiolitis patients (mean 1101 pg/mL) than in controls (2203 pg/mL, P < 0.001) but did not correlate with clinical severity. No correlation was found between serum sRAGE and severity score, respiratory viruses, and recurrent wheezing at 1 year. Serum sRAGE levels were negatively correlated with age (r = −0.45, P < 0.001).

Conclusion

Serum sRAGE levels are decreased in acute bronchiolitis but not correlated with disease severity. sRAGE levels should be age‐adjusted in infants. Serum sRAGE levels measured in the setting of acute bronchiolitis were not predictive of recurrent wheezing.

     

Increased severity of respiratory syncytial virus airway infection due to passive smoke exposure

Objective

Aim of this study was to analyze whether children with objectively measured second‐hand cigarette smoke (SHS) exposure suffer from a more severe course of disease when hospitalized with lower respiratory tract infection (LRTI) due to respiratory syncytial virus (RSV).

Methods

This prospective study was conducted at the Department of Pediatrics, Wilhelminen‐Hospital, Vienna, Austria in children aged below 1 year without a history of preceding lung disease and with acute symptoms of LRTI and a positive nasopharyngeal swab for RSV. On admission, urinary cotinine was measured as a marker of recent SHS and clinical severity of LRTI was assessed by oxygen saturation SpO₂ and the “admission clinical severity score” (CSSA). Parents/caregivers were asked to complete a customized questionnaire assessing risks for SHS and demographic characteristics.

Results

After inclusion of 217 patients, data of 185 patients with a mean (SD) age of 106 days (80) were analyzed. Twenty‐five patients (13.5%) were “cotinine‐positive” (COT+) defined as a urinary cotinine level of ≥7 μg/L. SpO₂ on admission was significantly lower in children recently exposed to SHS defined objectively by COT+ (94.8% ±2.0) in urine on admission compared to children not recently exposed (COT−) (96.8% ±3.0; P < 0.01). Disease severity, assessed via mean clinical severity score on admission (CSSA) for COT+ and COT− was 2.56 and 1.71, respectively (P = 0.03).

Conclusions

Recent exposure to SHS was associated with lower O₂ saturation and higher clinical severity score, measured by urine cotinine levels in children hospitalized for RSV infection under 1 year of age.

     

Outcome evaluation of a pharmacy‐based therapy management program for patients with cystic fibrosis

Objective

To compare medication adherence, pulmonary exacerbations, healthcare utilization, and costs for patients with cystic fibrosis (CF) who utilized a pharmacy‐based therapy management program to a matched control group. We hypothesized that patient management services would be associated with better medication adherence, and thus require fewer visits to the emergency room or hospitalizations.

Methods

This retrospective, observational cohort study used claims data from the MORE² claims Registry®. The sample consisted of CF patients, aged 6+, who had ≥1 pharmacy claim for inhaled tobramycin, inhaled aztreonam, ivacaftor, or dornase alfa from 6/2/2014‐5/31/2015. Adherence was measured as proportion of days covered (PDC). Propensity score matching and multivariable regression techniques were used to compare outcomes in program participants to matched controls.

Results

Of the 236 intervention and 724 control patients meeting selection criteria, 202 were propensity‐matched from each cohort. Relative to the control cohort, program patients had 23% higher mean PDC for tobramycin (IRR = 1.23, P = 0.01) and were twice as likely to be adherent to tobramycin (PDC ≥ 80%) than matched controls (OR = 2.14, P = 0.04). Program patients had fewer ER visits (IRR = 0.52, P < 0.01) and slightly lower ER costs (IRR = 0.66, P = 0.06) than the control patients.

Conclusion

A pharmacy‐based therapy management program for CF patients was associated with higher adherence to inhaled tobramycin and lower ER rates. Pharmacies that provide therapy management can support effective CF care management.

     

Pulmonary presentation of Kawasaki disease—A diagnostic challenge

Objectives

Kawasaki disease (KD) is a multisystemic vasculitis with predominant mucocutaneous manifestations. Pulmonary involvement in KD is distinctly uncommon and is not commonly recognized. We describe our experience of managing children with KD wherein the initial presentation was predominantly pulmonary.

Methods

Six hundred and two children have been diagnosed with KD during the period January 1993 to May 2017 in the Allergy Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh. Data were collected from inpatient records in Allergy Immunology Unit and follow‐up files in the Pediatric Rheumatology Clinic.

Results

Of 602 children, 11 (1.83%) had a predominant pulmonary presentation of KD. Mean age at diagnosis of KD was 2.5 years. Fever, cough and respiratory distress were the presenting complaints in all patients. First sign of KD was noted at a mean duration of 14.5 days from the onset of symptoms. Periungual desquamation was the most common clinical sign (72.7%). Persistent fever in spite of antimicrobials, thrombocytosis, and elevated erythrocyte sedimentation rate and C‐reactive protein levels pointed toward a diagnosis of KD in our patients. Parenchymal consolidation was evident on chest X‐ray in all patients, pleural effusion in six, empyema in three, and pneumothorax in two patients. Coronary artery abnormalities were evident in three patients. Intravenous immunoglobulin was given after a mean period of 22.4 days of onset of fever.

Conclusions

The diagnosis of KD is often delayed in children who have a predominantly pulmonary presentation. This can have adverse clinical consequences.

     

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.

     

Associations between maternal mental health and early child wheezing in a South African birth cohort

Background

Wheezing in early childhood is common and has been identified in high‐income countries (HIC) as associated with maternal antenatal or postnatal psychosocial risk factors. However, the association between maternal mental health and childhood wheezing has not been well studied in low and middle‐income countries (LMIC), such as South Africa.

Methods

A total of 1137 pregnant women over 18 year old, between 20 and 28 weeks’ gestation, and attending either of two catchment area clinics were enrolled in a South African parent study, the Drakenstein Child Health Study (DCHS). Psychosocial risk factors including maternal depression, psychological distress, early adversity, and intimate partner violence (IPV), were measured antenatally and postnatally by validated questionnaires. Two outcomes were evaluated: Presence of wheeze (at least one episode of child wheeze during the first 2 years of life); and recurrent wheeze (two or more episodes of wheezing in a 12‐month period). Logistic regression was used to investigate the association between antenatal or postnatal psychosocial risk factors and child wheeze, adjusting for clinical and socio‐demographic covariates.

Results

Postnatal psychological distress and IPV were associated with both presence of wheeze (adjusted OR = 2.09, 95%CI: 1.16‐3.77 and 1.63, 95%CI: 1.13‐2.34, respectively), and recurrent child wheeze (adjusted OR = 2.26, 95%CI: 1.06‐4.81 and 2.20, 95%CI: 1.35‐3.61, respectively).

Conclusion

Maternal postnatal psychological distress and IPV were associated with wheezing in early childhood. Thus, screening and treatment programs to address maternal psychosocial risk factors may be potential strategies to reduce the burden of childhood wheeze in LMICs.

     

Serologically diagnosed acute human bocavirus 1 infection in childhood community‐acquired pneumonia

Aim

To assess the role of human bocavirus 1 (HBoV1) as a causative agent of non‐severe community‐acquired pneumonia (CAP) in children.

Methods

Patients aged 2‐59 months with non‐severe CAP (respiratory complaints and radiographic pulmonary infiltrate/consolidation) attending a University Hospital in Salvador, Brazil were enrolled in a prospective cohort. From 820 recruited children in a clinical trial ( ClinicalTrials.gov NCT01200706), nasopharyngeal aspirate (NPA), and acute and convalescent serum samples were obtained from 759 (92.6%) patients. NPAs were tested for 16 respiratory viruses by PCR. Acute HBoV1 infection was confirmed by measuring specific IgM and IgG responses in paired serum samples.

Results

Respiratory viruses were detected in 693 (91.3%; 95%CI: 89.1‐93.2) CAP cases by PCR. HBoV1‐DNA was detected in 159 (20.9%; 95%CI: 18.2‐24.0) cases. Of these 159 PCR positive cases, acute HBoV1 infection was confirmed serologically in 38 cases (23.9%; 95%CI: 17.8‐31.0). Overall, acute HBoV1 infection was confirmed in 5.0% (38/759) of non‐severe CAP patients. HBoV1 was detected in 151 cases with at least one other virus making 31.7% of all multiple virus (n = 477) detections. Among all 759 cases, 216 had one respiratory virus detected, and sole HBoV1 was detected in only 8 (3.7%). Acute HBoV1 infection was serologically diagnosed in 34 (22.5%) HBoV1‐DNA‐positive cases with another virus, compared to 4 (50.0%) cases with sole virus detection (p = 0.09).

Conclusion

HBoV1 was detected by PCR in one fifth of the children with non‐severe CAP and acute HBoV1 infection was serologically confirmed in one quarter of these cases.

     

Nitric oxide‐releasing microparticles as a potent antimicrobial therapeutic against chronic rhinosinusitis bacterial isolates

Background

Bacteria, particularly in the biofilm state, may be implicated in the pathogenesis of chronic rhinosinusitis (CRS) and enhance antibiotic resistance. Nitric oxide (NO) is a gaseous immunomodulator with antimicrobial activity and a short half‐life, complicating achievement of therapeutic concentrations. We hypothesized that a novel microparticle‐based delivery platform, which allows for adjustable release of NO, could exhibit potent antibacterial effects.

Methods

Porous organosilica microparticles (SNO‐MP) containing nitrosylated thiol groups were formulated. Dissociation of the nitrosothiol groups generates NO at body temperature. The susceptibility of bacterial isolates from CRS patients to SNO‐MP was evaluated through a colony forming unit (CFU) assay. Serial dilutions of SNO‐MP in triplicate were incubated with isolates in suspension for 6 hours followed by plating on tryptic soy agar and overnight incubation followed by CFU quantification. Statistical analysis was performed with SPSS using one‐way analysis of variance with Bonferroni correction.

Results

SNO‐MP displayed antibacterial activity against gram‐positive (methicillin‐resistant and ‐sensitive Staphylococcus aureus) and gram‐negative (Pseudomonas aeruginosa, Enterobacter aerogenes, and Proteus mirabilis) isolates. SNO‐MP induced dose‐dependent reductions in CFU across all strains. Compared with controls and blank nanoparticles, SNO‐MP (10 mg/mL) induced a 99.99%‐100% reduction in CFU across all isolates, equivalent to a 5–9 log kill (p < 0.005). There was no statistically significant difference in CFU concentration between controls and blank microparticles.

Conclusion

SNO‐MP demonstrates potent bactericidal effect against antibiotic‐resistant CRS bacterial strains.

     

Stenotrophomonas maltophilia: A marker of lung disease severity

Background

While the prevalence of Stenotrophomonas maltophilia lung infection in cystic fibrosis (CF) patients has increased in the last decades, its pathogenicity remains controversial. The aim of this study was to investigate the effects of S. maltophilia initial infection on the progression of lung disease in CF children.

Methods

This case‐control retrospective study took place in a pediatric CF center. A total of 23 cases defined by at least one sputum culture positive for S. maltophilia, were matched for age, sex, and CFTR mutations to 23 never infected CF controls. The clinical data were collected for 2 years before and after S. maltophilia initial infection and comprised lung function analyses, rates of exacerbations and of antibiotic courses.

Results

Compared with controls, cases had lower lung function (P = 0.05), more frequent pulmonary exacerbations (P = 0.01), hospitalizations (P = 0.02), and intravenous antibiotic courses (P = 0.04) before S. maltophilia acquisition. In the year following S. maltophilia initial infection, lung function decline was similar in cases and controls but cases remained more severe, with more frequent pulmonary exacerbations (P = 0.01), hospitalizations (P = 0.02) and intravenous antibiotic courses (P = 0.02).

Conclusions

S. maltophilia seems to be a marker of CF lung disease severity and international recommendations to reduce lung infection by this pathogen should rapidly emerge.

     

Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis–associated interstitial lung disease are not predictive of disease progression

Objective

To evaluate the prognostic value of bronchoalveolar lavage (BAL) cellular profiles in patients with systemic sclerosis–associated interstitial lung disease (SSc‐ILD).

Methods

BAL cellularity was examined in relation to mortality (n = 141), serial pulmonary function findings (n = 134), and “progression‐free survival” (n = 134), by proportional hazards analysis. Baseline severity was quantified according to the extent of disease on high‐resolution computed tomography, the diffusing capacity for carbon monoxide, and the presence or absence of pulmonary hypertension. Mortality was subclassified into overall mortality (during 10 years of followup), early mortality (occurring within 2 years of presentation), and late mortality (occurring 2–10 years after presentation).

Results

Overall mortality was associated with neutrophilia on BAL (hazard ratio 2.23 [95% confidence interval 1.20–4.14], P = 0.01), but this effect was lost when disease severity was taken into account. Early mortality was associated with neutrophilia on BAL (hazard ratio 8.40 [95% confidence interval 1.91–36.95], P = 0.005), independent of disease severity. Late mortality was not associated with neutrophilia on BAL. The presence of neutrophilia on BAL was not associated with time to decline in pulmonary function or progression‐free survival. Neither eosinophilia nor lymphocytosis on BAL was associated with mortality, rapidity of functional deterioration, or progression‐free survival. These findings were unaltered when treatment status was taken into account.

Conclusion

BAL findings provide only limited prognostic information in SSc‐ILD. Neutrophilia on BAL is linked to early mortality, but BAL findings are not linked to long‐term survival or the rapidity of progression of lung disease. The usefulness of BAL to define alveolitis in SSc is questionable.

     

Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants

Background

The objective was to develop a risk scoring tool which predicts respiratory syncytial virus hospitalisation (RSVH) in moderate‐late preterm infants (32‐35 weeks’ gestational age) in the Northern Hemisphere.

Methods

Risk factors for RSVH were pooled from six observational studies of infants born 32 weeks and 0 days to 35 weeks and 6 days without comorbidity from 2000 to 2014. Of 13 475 infants, 484 had RSVH in the first year of life. Logistic regression was used to identify the most predictive risk factors, based on area under the receiver operating characteristic curve (AUROC). The model was validated internally by 100‐fold bootstrapping and externally with data from a seventh observational study. The model coefficients were converted into rounded multipliers, stratified into risk groups, and number needed to treat (NNT) calculated.

Results

The risk factors identified in the model included (i) proximity of birth to the RSV season; (ii) second‐hand smoke exposure; and (iii) siblings and/or daycare. The AUROC was 0.773 (sensitivity: 68.9%; specificity: 73.0%). The mean AUROC from internal bootstrapping was 0.773. For external validation with data from Ireland, the AUROC was 0.707 using Irish coefficients and 0.681 using source model coefficients. Cut‐off scores for RSVH were ≤19 for low‐ (1.0%), 20‐45 for moderate‐ (3.3%), and 50‐56 (9.5%) for high‐risk infants. The high‐risk group captured 62.0% of RSVHs within 23.6% of the total population (NNT 15.3).

Conclusions

This risk scoring tool has good predictive accuracy and can improve targeting for RSVH prevention in moderate‐late preterm infants.

     

Chronic kidney disease and coronary artery calcification in the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil)

Background

Chronic kidney disease is a worldwide public health concern due to the increased prevalence the high fatalities related to heart disease in this population. Among novel cardiovascular risk markers, the coronary artery calcification score (CAC) emerged as an independent predictor of cardiovascular events.

Hypothesis

We aimed to test if glomerular filtration rate or albuminuria are independently associated with coronary calcification.

Methods

The Brazilian Longitudinal Study of Adult Health is a cohort of men and women aged 35 to 74 years old addressing cardiovascular diseases. We analyzed the association of CAC, estimated glomerular filtration rate (eGFR), albumin‐to‐creatinine ratio (ACR) according to stages of eGFR (1 = ≥90; 2 = 60–89; 3 = <60 mL/min/1.73 m²), and ACR (<30; 30 to 300; >300 mg/g). These associations were estimated by logistic regression with a model including age, sex, race, income, and cardiovascular risk factors.

Results

Among 4189 persons (median age = 51 years, 54% women), 1183 had CAC. The odds ratio (OR) and the 95% confidence interval (95% CI) in the multivariate model was 0.86 (0.58‐1.29) for the category of eGFR <60 mL/min/1.73 m² compared to people with eGFR >90 mL/min/1.73m². On the other hand, the OR (95% CI) for individuals with ACR >300 mg/g was 4.31 (1.27‐14.64) compared to people with ACR <30 mg/g. A discrete interaction factor for the association with CAC between eGFR and ACR were analyzed as continuous variable.

Conclusions

Albuminuria was independently associated with coronary calcification, but the reduction of the glomerular filtration rate was not associated with CAC score in this sample of apparently healthy adults.

     

Long‐term use of continuous positive airway pressure therapy in coronary artery disease patients with nonsleepy obstructive sleep apnea

Background

Excessive daytime sleepiness is a frequent symptom of obstructive sleep apnea (OSA) and has been proposed as a motivator for adherence to continuous positive airway pressure (CPAP) therapy. However, excessive daytime sleepiness is absent in many patients with coronary artery disease (CAD) and concomitant OSA. We evaluated long‐term use of CPAP and predictors of CPAP use in nonsleepy and sleepy OSA patients from a CAD cohort.

Hypothesis

Long‐term CPAP use is lower in CAD patients with nonsleepy OSA vs sleepy OSA.

Methods

Nonsleepy (Epworth Sleepiness Scale [ESS] score < 10) OSA patients randomized to CPAP (n = 122) and sleepy (ESS ≥10) OSA patients offered CPAP (n = 155) in the RICCADSA trial in Sweden were included in this substudy. The median follow‐up was 4.8 years for the main trial, with a predefined minimum follow‐up of 2 years.

Results

The probability of remaining on CPAP at 2 years was 60% in nonsleepy patients and 77% in sleepy patients. Multivariate analyses indicated that age and hours of CPAP use per night at 1 month were independently associated with long‐term CPAP use in nonsleepy patients. In the sleepy phenotype, body mass index, acute myocardial infarction at baseline, and hours of CPAP use per night at 1 month were predictors of long‐term CPAP use.

Conclusions

Long‐term use of CPAP is likely to be challenging for CAD patients with nonsleepy OSA. Early CPAP use is an important predictor of continued long‐term use of CPAP, so optimizing patients' initial experience with CPAP could promote adherence.

     

Minimum Performance on Clinical Tests of Physical Function to Predict Walking 6,000 Steps/Day in Knee Osteoarthritis: An Observational Study

Objective

Evidence of physical function difficulties, such as difficulty rising from a chair, may limit daily walking for people with knee osteoarthritis (OA). The purpose of this study was to identify minimum performance thresholds on clinical tests of physical function predictive to walking ≥6,000 steps/day. This benchmark is known to discriminate people with knee OA who develop functional limitation over time from those who do not.

Methods

Using data from the Osteoarthritis Initiative, we quantified daily walking as average steps/day from an accelerometer (Actigraph GT1M) worn for ≥10 hours/day over 1 week. Physical function was quantified using 3 performance‐based clinical tests: 5 times sit‐to‐stand test, walking speed (tested over 20 meters), and 400‐meter walk test. To identify minimum performance thresholds for daily walking, we calculated physical function values corresponding to high specificity (80–95%) to predict walking ≥6,000 steps/day.

Results

Among 1,925 participants (mean ± SD age 65.1 ± 9.1 years, mean ± SD body mass index 28.4 ± 4.8 kg/m², and 55% female) with valid accelerometer data, 54.9% walked ≥6,000 steps/day. High specificity thresholds of physical function for walking ≥6,000 steps/day ranged 11.4–14.0 seconds on the 5 times sit‐to‐stand test, 1.13–1.26 meters/second for walking speed, or 315–349 seconds on the 400‐meter walk test.

Conclusion

Not meeting these minimum performance thresholds on clinical tests of physical function may indicate inadequate physical ability to walk ≥6,000 steps/day for people with knee OA. Rehabilitation may be indicated to address underlying impairments limiting physical function.

     

Pharmacokinetics and safety of paclitaxel delivery into porcine airway walls by a new endobronchial drug delivery catheter

Background and objective

Intratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side‐effect profiles are poorly understood.

Methods

Bronchial wall injection of generic paclitaxel (PTX) (102 injections of 0.05, 0.5, 1.5 or 2.5 mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5 mg/mL in 4 healthy pigs) was performed with a microneedle infusion catheter. Local histopathology, plasma and tissue PTX concentrations were evaluated at 7, 20 or 28 days post‐injection.

Results

Injection of generic PTX directly into the bronchial wall at doses up to 1.5 mg/mL only caused minimal tissue injury. Dose‐limiting tissue reaction was observed at 2.5 mg/mL. Plasma PTX was detectable for up to 5 days but not at 28 days, with area under the curve (AUC)_(0‐5d) 20‐ to 50‐fold lower than the AUC_(0‐∞) of 6300 ng h/mL for the approved intravenous dose. At 7 and 28 days post‐injection, bronchial PTX tissue concentrations were above a 10‐nmol/L cancer therapeutic level. PTX was not found in peripheral tissues. Similar results were observed between ABX and generic PTX.

Conclusion

Results of these studies confirm the administration of PTX directly into the bronchial wall is safe and feasible. PTX was detectable in plasma for <7 days but tissue concentrations remained therapeutic throughout the follow‐up period.

     

Long Term Effect of Intensive Lifestyle Intervention on Cerebral Blood Flow

Objectives

To determine whether long‐term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF ) in individuals with type 2 diabetes mellitus.

Design

Postrandomization assessment of CBF.

Setting

Action for Health in Diabetes multicenter randomized controlled clinical trial.

Participants

Individuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310).

Interventions

A multidomain intensive lifestyle intervention (ILI ) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE ), a control condition.

Measurements

Participants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI ) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization.

Results

Weight changes from baseline to time of MRI averaged ?6.2% for ILI and ?2.8% for DSE (P < .001), and increases in self‐reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL /100 g per minute, 95% confidence interval (CI ) = 0.07–6.70 mL /100 g per minute) and occipital lobes (3.52 mL /100 g per minute, 95% CI = 0.20–6.84 mL /100 g per minute). In ILI , greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02).

Conclusions

Long‐term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF .

     

Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis

Background

Lung transplantation has revolutionized the treatment of end‐stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft.

Methods

This is a single‐institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre‐ and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed.

Results

A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre‐ and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin‐resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001).

Conclusion

There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes.