Respiratory Exacerbations Research Articles

Association between Cough and Ambient Polycyclic Aromatic Hydrocarbons in Patients with Chronic Cough: An Observational Study in Two Regions of Japan

Ambient polycyclic aromatic hydrocarbons’ (PAHs) specific components are likely involved in respiratory disease development and exacerbation in children and adults. Airborne PAH exposure’s effects on cough symptoms in children and adults with chronic coughs in Kanazawa and Fukuoka, Japan, were investigated in this longitudinal study. A total of 98 patients with chronic coughs were enrolled and followed up between 1 April and 31 May 2020. The enrolled patients were non-smoking adults and children aged 3–83 years. Cough diaries were used to record and collect daily cough symptoms. High-performance liquid chromatography coupled with a fluorescence detector was used to determine the particulate PAH content in daily total suspended particles collected on quartz fiber filters. Ambient concentrations of fine particulate matter, nitrogen dioxide, and sulfur dioxide were obtained from local monitoring sites. Generalized estimated equations were used to estimate the association between daily PAHs and cough symptoms. Among nine PAHs measured, benz[a]anthracene (BaA) was significantly associated with cough symptoms for both lag4 and lag5 PAH exposure. These findings suggest that airborne specific PAHs, especially BaA, affect cough symptoms in children and adults with chronic cough. Further studies are needed to develop effective measures to prevent respiratory diseases against specific PAHs.

Xenon-enhanced dual-energy tomosynthesis for functional imaging of respiratory disease-Concept and phantom study.

Xenon-enhanced dual-energy (DE) computed tomography (CT) and hyperpolarized noble-gas magnetic resonance imaging (MRI) provide maps of lung ventilation that can be used to detect chronic obstructive pulmonary disease (COPD) early in its development and predict respiratory exacerbations. However, xenon-enhanced DE-CT requires high radiation doses and hyper-polarized noble-gas MRI is expensive and only available at a handful of institutionsglobally. To present xenon-enhanced dual-energy tomosynthesis (XeDET) for low-dose, low-cost functional imaging of respiratory disease in an experimental phantomstudy. We propose using digital tomosynthesis to produce Xe-enhanced low-energy (LE) and high-energy (HE) coronal images. DE subtraction of the LE and HE images is used to suppress soft tissues. We used an imaging phantom to investigate image quality in terms of the area under the reciever operating characteristic curve (AUC) for the Non-PreWhitening model observer with an Eye filter and internal noise (NPWEi). The phantom simulated anatomic clutter due to lung parenchyma and attenuation due to soft tissue and lung tissue. Aluminum slats were used to simulate rib structures. A stepwedge consisting of an acrylic casing with sealed cylindrical air-filled cavities was used to simulate ventilation defects with step thicknesses of 0.5, 1, and 2cm and cylindrical radii of 0.5, 0.75, and 1cm. The phantom was ventilated with Xe and projection data were acquired using a flat-panel detector, a tube-voltage combination of 60/140kV with 1.2 mm of copper filtration on the HE spectrum and an angular range of in 1° increments. The AUC of a NPWEi observer that has access only to a single coronal slice was calculated from measurements of the three-dimensional noise power spectrum and signal template. The AUC was calculated as a function of ventilation defect thickness and radius for total patient entrance air kermas ranging from 1.42 to 2.84mGy with and without rib-simulating Al slats. For the AUC analysis, the observer internal noise level was obtained from an ad hoc calibration to a high-dose dataset. XeDET was able to suppress parenchyma-simulating clutter in coronal images enabling visualization of the simulated ventilation defects, but the limited angle acquisition resulted in residual clutter due to out-of-plane bone-mimmicking structures. The signal power of the defects increased linearly with defect radius and showed a ten-fold to fifteen-fold increase in signal power when the defect thickness increased from 0.5 to 2cm. These trends agreed with theoretical predictions. Along the depth dimension, the power of the defects decreased exponentially with distance from the center of the defects with full-width half maxima that varied from 1.85to 2.85cm depending on the defect thickness and radius. The AUCs of the 1-cm-radius defect that was 2cm in thickness ranged from good (0.8-0.9) to excellent (0.9-1.0) over the range of air kermasconsidered. Xenon-enhanced DE tomosynthesis has the potential to enable functional imaging of respiratory disease and should be further investigated as a low-cost alternative to MRI-based approaches and a low-dose alternative to CT-basedapproaches.

Immunomodulators Containing Epicor, Colostrum, Vitamin D, Zinc, Lactobacilli and Bifidobacterium Reduce Respiratory Exacerbations in Children and Adults with Chronic Pulmonary Diseases

(1) Background: A number of studies have demonstrated the connection between developing or exacerbating chronic respiratory diseases in adults and children. However, still, few studies focus on reducing exacerbations via immunomodulation. (2) Methods: In this pilot study, a total of 25 pediatric and adult patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD)/persistent bacterial bronchitis (PBB) were included, administered over-the-counter (OTC) immunomodulators and followed up for 6 or 12 months. (3) Results: We observed a decrease in the frequency of exacerbations with slight improvements in functional respiratory indicators in adults on their second and third visits and a reduced number of exacerbations and improved spirometry indices in children with BA, although exacerbations requiring hospital admission remained at a similar rate. (4) Conclusions: We confirmed that the number of exacerbations of underlying chronic respiratory disease in adults and children could be reduced after the administration of OTC immunomodulators, probably by optimizing the immune resistance to common viral infections.

Lockdown Fatigue in Pediatric Respiratory Patients: Lessons from the First COVID-19 Year.

Lockdown policies have been implemented worldwide to limit the spread of COVID-19. "Lockdown fatigue" is a state of exhaustion related to the accumulating effects of repeated lockdowns. The aim of the current study was to examine the effects of repeated lockdowns on children with respiratory disorders. Data on children aged 0-18 years old with respiratory disorders were collected by an electronic survey during the third lockdown in Israel. The retrieved information included demographics and baseline medical status, respiratory clinical status during the third lockdown compared to pre-lockdown periods, lockdown adherence, lifestyle modifications and caregiver emotional status. The results were compared to those of a similar questionnaire distributed during the first lockdown. A total of 234 patients (62% males, 37% females, mean age 6.8 years (confidence interval 6.1-7.5)) were enrolled. Respiratory symptoms and exacerbation frequency were reduced in 76 (35.5%) and 58 (27.4%) patients, respectively, compared to the pre-lockdown period and similar to the first lockdown (p = 0.840 and p = 0.063, respectively). However, compared to the first lockdown, the third lockdown was associated with greater use of reliever medications (p = 0.006), less use of inhaled corticosteroids as routine treatment (p = 0.027), and more pediatric emergency room visits and hospitalizations (p = 0.001 and p < 0.001, respectively). The results also showed an increase in sedentary lifestyle (e.g., reduced physical activity (p = 0.025), less healthy eating habits (p = 0.001)) and reduced adherence to lockdown policies (p < 0.001). These data show that the continuing stability of clinical improvement during lockdown was accompanied by deleterious sequelae that potentially indicate "lockdown fatigue" among children with respiratory disorders.

The association of fecal calprotectin and respiratory exacerbation in cystic fibrosis patients

BackgroundCF patients experience several episodes of pulmonary exacerbations and reduction in their lung function progressively. Lung function is not the only diagnostic index by physicians to decide if CF patients require antibiotic therapy following pulmonary exacerbations. Non-invasive fecal indicators are increasingly being used to assess intestinal inflammation. Calprotectin is the most extensively utilized fecal biomarker in recent CF researches.MethodsIn this longitudinal study, 30 CF patients (1–18 years) without current infectious gastroenteritis were recruited from Mofid Children's Hospital and Masih Daneshvari Hospital, Tehran, Iran. Then, fecal calprotectin levels were evaluated before treatment, two weeks after systemic antibiotic administration, as well as recurrence of pulmonary exacerbation after first post-hospital discharge.ResultsThe initial fecal calprotectin level in CF patients receiving antibiotics was 651.13 ± 671.04, significantly decreasing two weeks after antibiotic therapy and following recurrence (171.81 ± 224.40, 607.93 ± 549.89, respectively; P < 0.01). Following systemic antibiotic treatment, the patient's respiratory and GI symptoms improved (P < 0.01).ConclusionOur findings revealed that fecal calprotectin modifications are associated with CF pulmonary exacerbations and antibiotic treatment could reduce calprotectin levels. Therefore, the fecal calprotectin level could be considered as a diagnostic tool and an index to follow the response to treatment in CF pulmonary exacerbations.

Divergent dynamics of inflammatory mediators and multiplex PCRs during airway infection in cystic fibrosis patients and healthy controls: Serial upper airway sampling by nasal lavage.

In cystic fibrosis (CF), acute respiratory exacerbations critically enhance pulmonary destruction. Since these mainly occur outside regular appointments, they remain unexplored. We previously elaborated a protocol for home-based upper airway (UAW) sampling obtaining nasal-lavage fluid (NLF), which, in contrast to sputum, does not require immediate processing. The aim of this study was to compare UAW inflammation and pathogen colonization during stable phases and exacerbations in CF patients and healthy controls. Initially, we obtained NLF by rinsing 10 ml of isotonic saline/nostril during stable phases. During exacerbations, subjects regularly collected NLF at home. CF patients directly submitted one aliquot for microbiological cultures. The remaining samples were immediately frozen until transfer on ice to our clinic, where PCR analyses were performed and interleukin (IL)-1β/IL-6/IL-8, neutrophil elastase (NE), matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1 were assessed. Altogether, 49 CF patients and 38 healthy controls (HCs) completed the study, and 214 NLF samples were analyzed. Of the 49 CF patients, 20 were at least intermittently colonized with P. aeruginosa and received azithromycin and/or inhaled antibiotics as standard therapy. At baseline, IL-6 and IL-8 tended to be elevated in CF compared to controls. During infection, inflammatory mediators increased in both cohorts, reaching significance only for IL-6 in controls (p=0.047). Inflammatory responses tended to be higher in controls [1.6-fold (NE) to 4.4-fold (MMP-9)], while in CF, mediators increased only moderately [1.2-1.5-fold (IL-6/IL-8/NE/TIMP-1/MMP-9)]. Patients receiving inhalative antibiotics or azithromycin (n=20 and n=15, respectively) revealed lower levels of IL-1β/IL-6/IL-8 and NE during exacerbation compared to CF patients not receiving those antibiotics. In addition, CF patients receiving azithromycin showed MMP-9 levels significantly lower than CF patients not receiving azithromycin at stable phase and exacerbation. Altogether, rhinoviruses were the most frequently detected virus, detected at least once in n=24 (49.0%) of the 49 included pwCF and in n=26 (68.4%) of the 38 healthy controls over the 13-month duration of the study. Remarkably, during exacerbation, rhinovirus detection rates were significantly higher in the HC group compared to those in CF patients (65.8% vs. 22.4%; p<0.0001). Non-invasive and partially home-based UAW sampling opens new windows for the assessment of inflammation and pathogen colonization in the unified airway system.

Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease.

Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease.

Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.

Inhaled anti-pseudomonal antibiotics for long-term therapy in cystic fibrosis.

Effect of Dornase Alfa on the Lung Clearance Index in Children with Cystic Fibrosis: A Lesson from a Case Series.

Dornase alfa (DNase) is the only mucus-degrading agent that has proven efficacy in cystic fibrosis (CF). Few studies have evaluated the effects of DNase on the lung clearance index (LCI). We report the experience of two CF centers in which LCI monitoring was used to evaluate the efficacy of DNase therapy. This is a prospective and observational study, evaluating the effects of DNase therapy on LCI values in three CF children followed at CF centers in Florence and Catania, Italy. In both centers, LCI was performed routinely, every 3-6 months, based on the clinical picture and severity of the lung disease. In this study, we evaluated the LCI before and after long-term DNase therapy. DNase improved LCI values in the absence of respiratory exacerbations: in case n. 1 LCI decreased by 39% in 16 months (from 11.1 to 6.8); in case n. 2 by 20% in 12 months (from 9.3 to 7.4); in case n. 3 by 24% in 16 months (from 9.3 to 7.0). This case series confirms the efficacy of DNase therapy in CF children, as demonstrated by the LCI reduction in treated patients. Furthermore, our results suggest that LCI is a sensitive marker of disease and can be used for the evaluation of response to treatment.

Nasopharynx microflora features and its role in the spread of nosocomial infection

Introduction. The threat of the spread of nosocomial infection is exacerbated by a number of factors, among which we should note the increase in the number of multidisciplinary medical institutions of various forms of ownership, the creation of new types of medical instruments, devices, medical drugs, the introduction of new kinds of invasive (instrumental) diagnostic and therapeutic interventions, the increase in the number of patients with suppressed immunity (premature newborns, patients with chronic diseases of various origins, elderly people). The source of nosocomial infection can be patients, medical personnel, visitors, and objects of the hospital environment: tools, linen, furniture, air, and food. The main ways of transmission of nosocomial infections are aerosol (air-droplet, air-dust), contact (through tools, linen, furniture), parenteral (when administering drugs), fecal-oral (dirty hands), alimentary (through food). Aim: to investigate the microflora of the nasopharynx of visitors to medical and preventive care institutions, to reveal the prevalence of carriers of pathogenic strains. The role of visitors to hospital patients in the spread of nosocomial infections is an extremely relevant topic, as it is insufficiently studied and requires in-depth research. Materials and methods. 40 visitors to medical and preventive care institutions (MPCI) who had no signs of respiratory tract diseases and exacerbations of comorbid pathologies were examined. All the studied visitors of MPCI patients were divided into 3 age groups according to WHO recommendations: 1st group (n=15) – young patients (18-44 years old); 2nd group (n=14) – middle-aged patients (44-60 years old); The 3rd group (n=11) – elderly patients (60-75 years old). Compliance of the distribution of clinical trial data with the law of normal distribution was checked using the Shapiro–Wilk test. Arithmetic means to value and standard error (M±m) were used to describe the data. The concentration of bacteria in the sample was presented as a decimal logarithm. The results. Bacteriogram indicators of the mucous membrane of the back wall of the nasopharynx were analyzed in visitors to the MPCI patients in different age groups. Statistically significant differences were found in the concentration of representatives of the studied bacteriogram (p˂0.05), which indicates the influence of age on the composition of the microflora of the mucous membrane of the back wall of the nasopharynx A statistically significant difference was established in the concentration and composition of representatives of the bacteriogram of the mucous membrane of the back wall of the nasopharynx in visitors to the MPCI patients of different age groups (p˂0.05), which indicates the dependence of the composition of the microflora of the nasopharynx on age. A statistically significantly higher concentration of Staphylococcus aureus was found in the group of young patients (p˂0.05), which indicates the release of the most significant amount of this pathogen from the carriers of this group and an increase in the probability of developing infectious complications when in contact with visitors to the hospital, who were included in the added group, in comparison with other studied groups. Conclusion. Asymptomatic carriers of pathogenic strains of bacteria were found in all studied age groups of visitors to the hospital, which suggests the possibility that the studied patients may be a potential source of hospital infection in hospital patients, but this requires further research.

Cancers pulmonaires associés à une pathologie interstitielle pulmonaire fibrosante

The occurrence of lung cancer in patients with diffuse fibrosing pneumonitis is neither fortuitous nor rare. Diagnosis strategy and therapeutics are currently poorly standardized, and there is no expert consensus available in Europe. Therapeutic strategy is limited by the poor underlying respiratory function, the risk of respiratory exacerbation favored by some treatments, age and comorbidities, and more generally by the underlying frailty of patients with lung fibrosis. In the current article we will review the epidemiology, the diagnosis management, and the necessary data for discussing local or systemic therapeutics.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Long term noninvasive ventilation and continuous positive airway pressure in children with neuromuscular diseases in France

The aim of the study was to describe the characteristics of children with neuromuscular diseases treated with long term noninvasive ventilation or continuous positive airway pressure in France. On June 1st 2019, 387 patients (63% boys, mean age 11.2 ± 5.5 years) were treated with long term noninvasive ventilation/continuous positive airway pressure. Thirty three percent of patients had spinal muscular atrophy, 30% congenital myopathy/dystrophy, 20% Duchenne muscular dystrophy, 7% Steinert myotonic dystrophy, and 9% other neuromuscular diseases. Ninety-four percent of patients were treated with long term noninvasive ventilation and 6% with continuous positive airway pressure. Treatment was initiated electively for 85% of patients, mainly on an abnormal overnight gas exchange recording (38% of patients). Noninvasive ventilation/continuous positive airway pressure was initiated during a respiratory exacerbation in 15% of patients. Mean duration of noninvasive ventilation/continuous positive airway pressure was 3.3 ± 3.1 years. Mean objective long term noninvasive ventilation/continuous positive airway pressure use was 8.0 ± 3.1 h/24. Spinal muscular atrophy, congenital myopathy/dystrophy, and Duchenne muscular dystrophy represented 83% of children with neuromuscular diseases treated with long term noninvasive ventilation in France. Screening for nocturnal hypoventilation was satisfactory as noninvasive ventilation /continuous positive airway pressure was predominantly initiated electively.

Monitoring disease progression in childhood bronchiectasis.

Bronchiectasis (not related to cystic fibrosis) is a chronic lung disease caused by a range of etiologies but characterized by abnormal airway dilatation, recurrent respiratory symptoms, impaired quality of life and reduced life expectancy. Patients typically experience episodes of chronic wet cough and recurrent pulmonary exacerbations requiring hospitalization. Early diagnosis and management of childhood bronchiectasis are essential to prevent respiratory decline, optimize quality of life, minimize pulmonary exacerbations, and potentially reverse bronchial disease. Disease monitoring potentially allows for (1) the early detection of acute exacerbations, facilitating timely intervention, (2) tracking the rate of disease progression for prognostic purposes, and (3) quantifying the response to therapies. This narrative review article will discuss methods for monitoring disease progression in children with bronchiectasis, including lung imaging, respiratory function, patient-reported outcomes, respiratory exacerbations, sputum biomarkers, and nutritional outcomes.

Preclinical evaluation of the epithelial sodium channel inhibitor AZD5634 and implications on human translation.

Airway dehydration causes mucus stasis and bacterial overgrowth in cystic fibrosis (CF), resulting in recurrent respiratory infections and exacerbations. Strategies to rehydrate airway mucus including inhibition of the epithelial sodium channel (ENaC) have the potential to improve mucosal defense by enhancing mucociliary clearance (MCC) and reducing the risk of progressive decline in lung function. In the current work, we evaluated the effects of AZD5634, an ENaC inhibitor that shows extended lung retention and safety profile as compared with previously evaluated candidate drugs, in healthy and CF preclinical model systems. We found that AZD5634 elicited a potent inhibition of amiloride-sensitive current in non-CF airway cells and airway cells derived from F508del-homozygous individuals with CF that effectively increased airway surface liquid volume and improved mucociliary transport (MCT) rate. AZD5634 also demonstrated efficacious inhibition of ENaC in sheep bronchial epithelial cells, translating to dose-dependent improvement of mucus clearance in healthy sheep in vivo. Conversely, nebulization of AZD5634 did not notably improve airway hydration or MCT in CF rats that exhibit an MCC defect, consistent with findings from a first single-dose evaluation of AZD5634 on MCC in people with CF. Overall, these findings suggest that CF animal models demonstrating impaired mucus clearance translatable to the human situation may help to successfully predict and promote the successful translation of ENaC-directed therapies to the clinic.

Identification of Modifiable Risk Factors of Exacerbations Chronic Respiratory Diseases with Airways Obstruction, in Vietnam.

Objectives: to determine modifiable risk factors of exacerbations in chronic respiratory diseases with airways obstruction (i.e., asthma and COPD) in southern Vietnam. Methods: an environmental and health-related behavioural questionnaire was submitted to patients with both chronic respiratory symptoms and airways obstruction. An exacerbation was defined as any acute worsening in clinical symptoms requiring a change in treatment, in a patient receiving prophylactic therapy. Results: 235 patients were evaluated, including 131 (56%) chronic obstructive pulmonary disease (COPD) and 104 (44%) asthmatics. There were 75% males and 69% smokers. Occupational exposure accounted for 66%, mainly among construction and industry workers. Smoking was associated with more severe airways obstruction. Respiratory exacerbations were reported in 56/235 patients (24%). The risk of exacerbation was increased in patients with a lower education level, exposure to occupational pollutants, cumulative smoking ≥ 20 pack year, housing space < 10 m2, and poorly ventilated housing. Based on multivariate analysis, the risk of exacerbation remained significantly higher among patients with occupational exposure and low housing space per person. Conclusions: besides smoking cessation, more supportive policies, including improvement of occupational environment and housing design for better ventilation, are needed to prevent the severity of chronic respiratory diseases in Vietnam.

Proactive Electronic Visits for Smoking Cessation and Chronic Obstructive Pulmonary Disease Screening in Primary Care: Randomized Controlled Trial of Feasibility, Acceptability, and Efficacy.

BackgroundMost smokers with chronic obstructive pulmonary disease (COPD) have not yet been diagnosed, a statistic that has remained unchanged for over two decades. A dual-focused telehealth intervention that promotes smoking cessation, while also facilitating COPD screening, could help address national priorities to improve the diagnosis, prevention, treatment, and management of COPD. The purpose of this study was to preliminarily evaluate an integrated asynchronous smoking cessation and COPD screening e-visit (electronic visit) that could be delivered proactively to adult smokers at risk for COPD, who are treated within primary care.ObjectiveThe aims of this study were (1) to examine e-visit feasibility and acceptability, particularly as compared to in-lab diagnostic pulmonary function testing (PFT), and (2) to examine the efficacy of smoking cessation e-visits relative to treatment as usual (TAU), all within primary care.MethodsIn a randomized clinical trial, 125 primary care patients who smoke were randomized 2:1 to receive either proactive e-visits or TAU. Participants randomized to the e-visit condition were screened for COPD symptoms via the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE). Those with scores ≥2 were invited to complete both home spirometry and in-lab PFTs, in addition to two smoking cessation e-visits. Smoking cessation e-visits assessed smoking history and motivation to quit and included completion of an algorithm to determine the best Food and Drug Administration–approved cessation medication to prescribe. Primary outcomes included measures related to (1) e-visit acceptability, feasibility, and treatment metrics; (2) smoking cessation outcomes (cessation medication use, 24-hour quit attempts, smoking reduction ≥50%, self-reported abstinence, and biochemically confirmed abstinence); and (3) COPD screening outcomes.ResultsOf 85 participants assigned to the e-visits, 64 (75.3%) were invited to complete home spirometry and in-lab PFTs based on CAPTURE. Among those eligible for spirometry, 76.6% (49/64) completed home spirometry, and 35.9% (23/64) completed in-lab PFTs. At 1 month, all cessation outcomes favored the e-visit, with a significant effect for cessation medication use (odds ratio [OR]=3.22). At 3 months, all cessation outcomes except for 24-hour quit attempts favored the e-visit, with significant effects for cessation medication use (OR=3.96) and smoking reduction (OR=3.09).ConclusionsA proactive, asynchronous e-visit for smoking cessation and COPD screening may offer a feasible, efficacious approach for broad interventions within primary care.Trial RegistrationClinicalTrials.gov NCT04155073; https://clinicaltrials.gov/ct2/show/NCT04155073

Intracellular replication of Inquilinus limosus in bronchial epithelial cells

Inquilinus limosus is an emerging multi-resistant opportunistic pathogen documented mainly in cystic fibrosis patients. Infection with I. limosus is accompanied by either an acute respiratory exacerbation or a progressive loss of pulmonary function. This study examined the interaction of Inquilinus limosus with the bronquial human epithelial cell line 16HBE14o−. Almost 100% of the bacteria that attached to the bronquial cells were found internalized and located in acidic LAMP2 positive compartments. According to confocal studies combined with antibiotic protection assays, I. limosus is able to survive and eventually replicate in these compartments. I. limosus was found nontoxic to cells and did not induce neither IL-6 nor IL-8 cytokine production, a characteristic that may help the bacteria to evade host immune response. Overall, this study indicates that I. limosus displays pathogenic properties based on its ability to survive intracellularly in epithelial cells eventually leading to antibiotic failure and chronic infection.

Long-term Azithromycin in Children With Bronchiectasis Unrelated to Cystic Fibrosis: Treatment Effects Over Time

Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown. (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect. Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P< .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR]= 0.81 [95%CI, 0.57-1.14] vs0.29 [0.20-0.44]; P< .001); New Zealand children (IRR= 0.73 [0.51-1.03] vs0.39 [0.28-0.55]; P= .012); and those with higher weight-for-height z scores (interaction IRR= 0.82 [0.67-0.99]; P= .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR= 0.41 [0.30-0.55] vs0.74 [0.49-1.10]; P= .012). Regular azithromycin is best used for at least 17weeks and up to 62weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice. Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.

Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry

To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49year (IQR, 0.21-1.77years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3years, associated with a diagnosis of pulmonary hypertension at age <6months (54% vs 29%; P=.002) and a pretricuspid shunt (65% vs 38%; P=.02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension. Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.

A Personalized Respiratory Disease Exacerbation Prediction Technique Based on a Novel Spatio-Temporal Machine Learning Architecture and Local Environmental Sensor Networks

Chronic respiratory diseases, such as the Chronic Obstructive Pulmonary Disease (COPD) and asthma, are a serious health crisis, affecting a large number of people globally and inflicting major costs on the economy. Current methods for assessing the progression of respiratory symptoms are either subjective and inaccurate, or complex and cumbersome, and do not incorporate environmental factors to track individualized risks. Lacking predictive assessments and early intervention, unexpected exacerbations often lead to hospitalizations and high medical costs. This work presents a multi-modal solution for predicting the exacerbation risks of respiratory diseases, such as COPD, based on a novel spatio-temporal machine learning architecture for real-time and accurate respiratory events detection, and tracking of local environmental and meteorological data and trends. The proposed new neural network model blends key attributes of both convolutional and recurrent neural architectures, allowing extraction of the salient spatial and temporal features encoded in respiratory sounds, thereby leading to accurate classification and tracking of symptoms. Combined with the data from environmental and meteorological sensors, and a predictive model based on retrospective medical studies, this solution can assess and provide early warnings of respiratory disease exacerbations, thereby potentially reducing hospitalization rates and medical costs.