Exacerbations Of Chronic Respiratory Disease Research Articles

Length of Hospital Stay and Its Predictions Among Patients With Exacerbations of Chronic Respiratory Diseases.

Chronic respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) may deteriorate into acute exacerbations requiring hospitalization. Assessing the predictors of prolonged hospital stays could help identify potential interventions to reduce the burden on patients and healthcare systems. This study aimed to identify the risk factors attributed to prolonged hospital stays among patients admitted with acute exacerbations of chronic respiratory disorders in Jordan. A retrospective cohort study was conducted by reviewing the demographic and clinical characteristics of hospitalized patients with asthma and COPD exacerbations between January 2017 and July 2021. The recorded variables were checked for their independence. Simple and stepwise multivariate linear regressions were then performed to identify variables associated significantly with a longer hospital length of stay (LOS). A total of 896 cases were evaluated. The mean ± SD stay was 5.66 ± 3.40 days, whereas the median (IQR) was 5.00 (4.00) days. Variables associated significantly with prolonged LOS in the multivariate analysis were female gender (β = 0.089, p = 0.011), pulmonary hypertension (β = 0.093, p = 0.004), allergic rhinitis (β = 0.086, p = 0.007), ICU admission (β = 0.096, p = 0.003), requirement for mechanical ventilation (β = 0.102, p = 0.002), higher total number of medications (β = 0.281, p < 0.001) and the number of exacerbation-related medications (β = 0.200, p < 0.001). However, smoking (β = -0.091, p = 0.008) was significantly associated with a shorter LOS. Gender, pulmonary hypertension, allergic rhinitis, ICU admission, mechanical ventilation, the number of medications and smoking were significantly related to LOS. These findings emphasize the importance of patients' demographics and their clinical status in determining LOS, hence providing protective interventions to shorten it.

Incidence of acute exacerbations of chronic respiratory disease during pulmonary rehabilitation delivered at home or hospital

Incidence of acute exacerbations of chronic respiratory disease during pulmonary rehabilitation delivered at home or hospital

Surgical methods of treatment for tibial diaphyseal fractures

Background. Bone fractures are a public health concern. In recent years, there has been an upward trend in body weight of people of all age groups. Obesity has long been thought to help protect against fractures, but recent studies have shown that for every 5 cm increase in waist circumference, the risk of any fracture is 3 % higher. The purpose: according to the meta-analysis of modern medical literature, to determine the main directions of surgical treatment for long bone fractures, their advantages, and disadvantages, including in overweight patients, the features of diaphyseal fracture fixation in overweight patients. Materials and methods. A meta-analysis of special literature from scientific databases was conducted: Cochrane Library, Scopus, National Library of Medicine — National Institutes of Health, ReLAB-HS Rehabilitation Resources Repository. One hundred and thirty articles were analyzed, from them 31 were selected, which, in our opinion, reflect the purpose of the study. Results. All methods of surgical fixation of fractures have their advantages and disadvantages. The frequency of nonunions caused by intramedullary fixation of the femoral shaft can reach 10 %, and varus/valgus and rotational deformities and shortening can also be observed. But the use of locking screws prevents the occurrence of most complications. When fixing the fractures with plates, the main complications are related to superficial and deep infections, which were more often observed in overweight patients. The analysis demonstrated that in overweight and obese patients, the main complicating factor is not the method for fixing the fracture zone, but factors related to the health of the patient himself. So, despite the fact that the results of treatment of fractures in patients with normal weight and obesity did not have a statistically significant difference, an increase in cardiovascular complications, exacerbation of chronic respiratory diseases was observed. Moreover, it is the presence of concomitant diseases that often makes surgical intervention impossible. Conclusions. There is a large amount of research on surgical methods of fixing tibial diaphyseal fractures, but data on the choice of fixation method in overweight and obese patients as a separate approach were not found. There are data on complicating factors of excess weight in the treatment of fractures and surgical interventions. Systematic studies related specifically to the algorithm for choosing the method of fracture fixation and complications have also not been found.

ARL5b inhibits human rhinovirus 16 propagation and impairs macrophage-mediated bacterial clearance

Human rhinovirus is the most frequently isolated virus during severe exacerbations of chronic respiratory diseases, like chronic obstructive pulmonary disease. In this disease, alveolar macrophages display significantly diminished phagocytic functions that could be associated with bacterial superinfections. However, how human rhinovirus affects the functions of macrophages is largely unknown. Macrophages treated with HRV16 demonstrate deficient bacteria-killing activity, impaired phagolysosome biogenesis, and altered intracellular compartments. Using RNA sequencing, we identify the small GTPase ARL5b to be upregulated by the virus in primary human macrophages. Importantly, depletion of ARL5b rescues bacterial clearance and localization of endosomal markers in macrophages upon HRV16 exposure. In permissive cells, depletion of ARL5b increases the secretion of HRV16 virions. Thus, we identify ARL5b as a novel regulator of intracellular trafficking dynamics and phagolysosomal biogenesis in macrophages and as a restriction factor of HRV16 in permissive cells.

Results of the prospective observation in routine practice of hypertensive patients with concomitant chronic respiratory diseases. Part II. Predictors of adverse events

Aim. To study the predictors of adverse events in hypertensive (HTN) patients, including those with chronic respiratory diseases (CRDs).Material and methods. Regression analysis evaluated clinical and anamnestic data and blood pressure (BP) in outpatients with stage II-III HTN (n=156): 49 patients had asthma, 20 — chronic obstructive pulmonary disease; age — 63,4±8,8 years, women — 72,4%, followup duration 29,3±8,0 months. The outcomes included in the composite primary endpoint (EP) were registered in 32 patients (death, major cardiovascular events and complications), while the secondary EPs were registered in 57 patients (hospitalizations, emergency calls, temporary disability due to cardiovascular disease/CRD, hypertensive crisis, exacerbation of CRD, pneumonia, respiratory failure), and tertiary EP — in 76 (other significant diseases/conditions, including increased blood pressure without hypertensive crisis, requiring correction of regular therapy).Results. Predictors of primary EPs were the decrease level of nocturnal diastolic BP (DBP) (β=-5,335, p=0,026), nocturnal DBP variability (β=1,796, p=0,007), blood leukocyte level (β=0,241, p=0,039); secondary EPs — systolic blood pressure ≥170 mm Hg in history (β=1,305-1,641, p=0,037-0,017), statin use (β=-0,997, p=0,037), CRD (β=0,734, p=0,023), blood platelet level (β=-0,008, p=0,022); tertiary EPs — only CRD (β=1,082, p&lt;0,0001).Conclusion. Patients with HTN need complex multifactorial prevention. It is necessary to improve the control of office and ambulatory blood pressure, blood lipids, especially in the presence of CRD, to improve the control of CRDs themselves. The method of 24-hour blood pressure monitoring should be used more often in routine practice, including assessing the degree of nocturnal blood pressure reduction and its variability.

Возможности профилактики обострений хронических заболеваний дыхательных путей

Control of virus-induced airway inflammation in patients with chronic bronchopulmonary disorders remains an urgent medical task. Managing the immune response in acute respiratory viral infections (ARVIs) in these patients is a promising area. This review summarizes the results of observational programs and initiative studies on the experience with a drug based on technologically processed antibodies in pulmonary practice. This drug is characterized by immune-mediated antiviral and antibacterial effects. The mechanism of its action implies the activation of antigen processing and presentation involving major histocompatibility complex molecules, which in turn contributes to an adequate immune response in the infectious process. Therefore, this drug can be used for treating ARVIs in patients with a high risk of unfavorable course of respiratory infections. Our findings demonstrate that this drug prevents the exacerbation of chronic bronchopulmonary disorders in ARVIs. Its inclusion in complex therapy for community-acquired pneumonia in patients with a higher risk of having resistant flora provided the completion of the treatment course without changing the antibiotic. KEYWORDS: chronic bronchopulmonary disorders, chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis, community- acquired pneumonia, antibiotic resistance. FOR CITATION: Prozorova G.G., Zaytsev A.A., Petrov V.A. Prevention of exacerbations of chronic respiratory diseases. Russian Medical Inquiry. 2023;7(8):524–528 (in Russ.). DOI: 10.32364/2587-6821-2023-7-8-8.

Partículas en suspensión PM10, NO2 y agudizaciones de enfermedad respiratoria crónica

The new World Health Organization guidelines recommend studies with simultaneous exposure to multiple air pollutants. The main objective has been to analyze the strength of the association between different concentrations of PM10 and NO2 and the exacerbation of chronic respiratory diseases (ECRD), specifically asthma and chronic obstructive pulmonary disease. Retrospective cross-sectional study. The population analyzed were adults treated in an urgent and primary health care center on certain lag+1 days in 2019. Three indices have been developed (1: high levels of PM10 and NO2; 2: high level of PM10 and low level of NO2, and 3: low levels of PM10 and NO2) and a logistic regression model for each of them, with ECRD as the outcome variable, and the progressive addition of adjustment variables (sex, age, tobacco, Charlson index, season, precipitation, wind and temperature). Four hundred and sixty-one people were analyzed, 17 with ECRD. Models 1 and 2 presented very similar values in the adjusted OR (4.28 [95% CI 1.05-17]), R2 (0.88) and the area under the ROC curve (>0.72). In both of them the significance was maintained after including the adjustment variables, while model 3 only allowed the addition of precipitation. The inclusion of the Charlson index and the tobacco consumption in the 3 models implied the loss of statistical significance of the PM10/NO2 combination regarding ECRD. High levels of PM10 are related to ECRD and have a greater impact than NO2, with tobacco use and comorbidities being the main precipitants of ECRD.

Air pollution induces Staphylococcus aureus USA300 respiratory tract colonization mediated by specific bacterial genetic responses involving the global virulence gene regulators Agr and Sae.

Exposure to particulate matter (PM), a major component of air pollution, is associated with exacerbation of chronic respiratory disease, and infectious diseases such as community-acquired pneumonia. Although PM can cause adverse health effects through direct damage to host cells, our previous study showed that PM can also impact bacterial behaviour by promoting in vivo colonization. In this study we describe the genetic mechanisms involved in the bacterial response to exposure to black carbon (BC), a constituent of PM found in most sources of air pollution. We show that Staphylococcus aureus strain USA300 LAC grown in BC prior to inoculation showed increased murine respiratory tract colonization and pulmonary invasion in vivo, as well as adhesion and invasion of human epithelial cells in vitro. Global transcriptional analysis showed that BC has a widespread effect on S. aureus transcriptional responses, altering the regulation of the major virulence gene regulators Sae and Agr and causing increased expression of genes encoding toxins, proteases and immune evasion factors. Together these data describe a previously unrecognized causative mechanism of air pollution-associated infection, in that exposure to BC can increase bacterial colonization and virulence factor expression by acting directly on the bacterium rather than via the host.

Access to highly specialized growth substrates and production of epithelial immunomodulatory metabolites determine survival of Haemophilus influenzae in human airway epithelial cells.

Haemophilus influenzae (Hi) infections are associated with recurring acute exacerbations of chronic respiratory diseases in children and adults including otitis media, pneumonia, chronic obstructive pulmonary disease and asthma. Here, we show that persistence and recurrence of Hi infections are closely linked to Hi metabolic properties, where preferred growth substrates are aligned to the metabolome of human airway epithelial surfaces and include lactate, pentoses, and nucleosides, but not glucose that is typically used for studies of Hi growth in vitro. Enzymatic and physiological investigations revealed that utilization of lactate, the preferred Hi carbon source, required the LldD L-lactate dehydrogenase (conservation: 98.8% of strains), but not the two redox-balancing D-lactate dehydrogenases Dld and LdhA. Utilization of preferred substrates was directly linked to Hi infection and persistence. When unable to utilize L-lactate or forced to rely on salvaged guanine, Hi showed reduced extra- and intra-cellular persistence in a murine model of lung infection and in primary normal human nasal epithelia, with up to 3000-fold attenuation observed in competitive infections. In contrast, D-lactate dehydrogenase mutants only showed a very slight reduction compared to the wild-type strain. Interestingly, acetate, the major Hi metabolic end-product, had anti-inflammatory effects on cultured human tissue cells in the presence of live but not heat-killed Hi, suggesting that metabolic endproducts also influence HI-host interactions. Our work provides significant new insights into the critical role of metabolism for Hi persistence in contact with host cells and reveals for the first time the immunomodulatory potential of Hi metabolites.

Acute Cough in Adult Patients

Acute cough (< 8 weeks) is a frequent complaint in family practice consultations. The most common cause are respiratory infections. The Guideline "Acute and chronic cough" of the German College of General Practitioners and Family Physicians (DEGAM) was updated in 2021 and contains recommendations for an evidence-based approach for the management of acute cough in primary care. The guideline has been updated in accordance with the findings of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed by an interdisciplinary guideline committee and agreed by formal consensus. History-taking, exclusion of red flags and a physical examination are the basis of diagnostic evaluation. If an acute, uncomplicated bronchitis is likely, no laboratory tests, sputum diagnostics, or chest x-rays should be performed, and antibiotics should not be administered. Evidence based strategies to avoid antibiotic therapy (delayed prescribing, shared decision making, point-of-care-tests) can be used. There is inadequate evidence for the efficacy of antitussive or expectorant drugs against acute cough. The state of the evidence for phytotherapeutic agents is heterogeneous; clinical importance is minimal. COVID-19 should currently be considered in cases of acute respiratory symptoms. If specific symptoms or red flags occur, further diagnoses in the context of acute cough such as community-acquired pneumonia, influenza disease and exacerbations of chronic respiratory diseases (bronchial asthma, COPD) should be taken into consideration. These evidence-based recommendations are intended to reduce the use of antibiotics to treat colds and acute bronchitis, for which they are not indicated. Further clinical trials of symptomatic treatments for cough should be performed in order to extend the evidence base.

Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections

Rhinovirus infection is common and usually causes mild, self-limiting upper respiratory tract symptoms. Rhinoviruses can cause exacerbation of chronic respiratory diseases, such as asthma or chronic obstructive pulmonary disease, leading to a significant burden of morbidity and mortality. There has been a great deal of progress in efforts to understand the immunological basis of rhinovirus infection. However, despite a number of in vitro and in vivo attempts, there have been no effective treatments developed. This review article summarises the up to date virological and immunological understanding of these infections. We discuss the challenges researchers face, and key solutions, in their work to investigate potential therapies including in vivo rhinovirus challenge studies. Finally, we explore past and present experimental therapeutic strategies employed in the treatment of rhinovirus infections and highlight promising areas of future work.

Association of diurnal temperature range with daily hospitalization for exacerbation of chronic respiratory diseases in 21 cities, China

BackgroundThe association between diurnal temperature range (DTR) and hospitalization for exacerbation of chronic respiratory diseases (CRD) was rarely reported.ObjectivesTo examine the association between DTR and daily hospital admissions for exacerbation of CRD and find out the potential effect of modifications on this association.MethodData on daily hospitalization for exacerbation of chronic obstructive pulmonary disease (COPD), asthma and bronchiectasis and meteorology measures from 2013 through 2017 were obtained from 21 cities in South China. After controlling the effects of daily mean temperature, relative humidity (RH), particulate matter < 2.5 μm diameter (PM2.5) and other confounding factors, a standard generalized additive model (GAM) with a quasi-Poisson distribution was performed to evaluate the relationships between DTR and daily hospital admissions of CRD in a two-stage strategy. Subgroup analysis was performed to find potential modifications, including seasonality and population characteristics.ResultElevated risk of hospitalization for exacerbation of CRD (RR = 1.09 [95%CI: 1.08 to 1.11]) was associated with the increase in DTR (the 75th percentile versus the 25th percentile of DTR at lag0–6). The effects of DTR on hospital admissions for CRD were strong at low DTR in the hot season and high DTR in the cold season. The RR (the 75th percentile versus the 25th percentile of DTR at lag0–6) of hospitalization was 1.11 (95%CI: 1.08 to 1.12) for exacerbations of COPD and 1.09 (95%CI: 1.05 to 1.13) for asthma. The adverse effect of DTR on hospitalization for bronchiectasis was only observed in female patients (RR = 1.06 [95%CI: 1.03 to 1.10]).ConclusionOur study provided additional evidence for the association between DTR and daily hospitalization for exacerbation of CRD, and these associations are especially stronger in COPD patients and in the cold season than the hot season. Preventive measures to reduce the adverse impacts of DTR were needed for CRD patients.

Potential link between compromised air quality and transmission of the novel corona virus (SARS-CoV-2) in affected areas

The emergence of a novel human corona virus disease (COVID-19) has been declared as a pandemic by the World Health Organization. One of the mechanisms of airborne transmission of the severe acute respiratory syndrome - corona virus (SARS-CoV-2) amid humans is through direct ejection of droplets via sneezing, coughing and vocalizing. Nevertheless, there are ample evidences of the persistence of infectious viruses on inanimate surfaces for several hours to a few days. Through a critical review of the current literature and a preliminary analysis of the link between SARS-CoV-2 transmission and air pollution in the affected regions, we offer a perspective that polluted environment could enhance the transmission rate of such deadly viruses under moderate-to-high humidity conditions. The aqueous atmospheric aerosols offer a conducive surface for adsorption/absorption of organic molecules and viruses onto them, facilitating a pathway for higher rate of transmission under favourable environmental conditions. This mechanism partially explains the role of polluted air besides the exacerbation of chronic respiratory diseases in the rapid transmission of the virus amongst the public. Hence, it is stressed that more ambitious policies towards a cleaner environment are required globally to nip in the bud what could be the seeds of a fatal outbreak such as COVID-19.

ELISA-Based Assay for Studying Major and Minor Group Rhinovirus-Receptor Interactions.

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, and the need for preclinical models for the screening of vaccine candidates and antiviral compounds. We report the establishment and characterization of an ELISA-based assay for studying major and minor group RV–receptor interactions. This assay is based on the interaction of purified virus with plate-bound human receptor proteins, intercellular adhesion molecule 1 (ICAM-1), and low density lipoprotein receptor (LDLR). Using RV strain-specific antibodies, we demonstrate the specific binding of a panel of major and minor RV group types including RV-A and RV-B strains to ICAM-1 and LDLR, respectively. We show that the RV–receptor interaction can be blocked with receptor-specific antibodies as well as with soluble receptors and neutralizing RV-specific antibodies. The assay is more sensitive than a cell culture-based virus neutralization test. The ELISA assay will therefore be useful for the preclinical evaluation for preventive and therapeutic strategies targeting the RV–receptor interaction, such as vaccines, antibodies, and anti-viral compounds.

MiR-29b-3p promotes particulate matter-induced inflammatory responses by regulating the C1QTNF6/AMPK pathway.

Inflammatory responses are considered to be the critical mechanism underlying particulate matter (PM)-induced development and exacerbation of chronic respiratory diseases. MiR-29b-3p has been found to participate in various biological processes, but its role in PM-induced inflammatory responses was previously unknown. Here, we constructed a miRNA PCR array to find that miR-29b-3p was the most highly expressed in human bronchial epithelial cells (HBECs) exposed to PM. MiR-29b-3p promoted PM-induced pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) expression via inhibiting the AMPK signaling pathway in HBECs. RNA sequencing and luciferase reporter assay identified that miR-29b-3p targeted complement C1q tumor necrosis factor-related protein 6 (C1QTNF6), a protein that protected from PM-induced inflammatory responses via activating the AMPK signaling pathway. In vivo, miR-29b-3p antagomirs delivered via the tail vein prior to PM exposure significantly counteracted PM-induced miR-29b-3p upregulation and C1QTNF6 downregulation in lung tissues. Furthermore, miR-29b-3p inhibition alleviated inflammatory cells infiltration and pro-inflammatory cytokines secretion in the lung of PM-exposed mice. These findings firstly revealed that miR-29b-3p acted as a novel modulator of PM-induced inflammatory responses by targeting the C1QTNF6/AMPK signaling pathway, which contributes to a better understanding of the biological mechanisms underlying adverse PM-induced respiratory health effects.

Outcomes of RV Dysfunction in Acute Exacerbation of Chronic Respiratory Diseases

Outcomes of RV Dysfunction in Acute Exacerbation of Chronic Respiratory Diseases

Effect of long-term clarithromycin therapy on prevention of pneumonia in older adults: A randomized, controlled trial.

Pneumonia in older adults is increasingly recognized as a healthcare issue in countries with an aging population. Long-term macrolide therapy reduces exacerbations of chronic respiratory diseases, but its effects on the prevention of pneumonia have not been determined. We carried out a randomized, controlled trial to test the effect of long-term clarithromycin therapy on the prevention of pneumonia among older adults. People aged ≥65 years who had recovered from pneumonia within the previous 3 months were recruited and randomly allocated to a long-term, low-dose clarithromycin (CAM) therapy group (n = 13) or a control group (n = 15). Both groups were followed up until recurrence of pneumonia. The median follow-up period was 251 days (95% CI 171-330) in the CAM group and 132 days (95% CI 67-196) in the control group (P = 0.627). The recurrence rate of pneumonia was two out of 13 (15%) in the CAM group and five out of 15 (33%) in the control group (P = 0.268). The median time to recurrence of pneumonia was 315 days (95% CI 249-382) in the CAM group and 260 days (95% CI 184-335) in the control group (P = 0.260). None of the differences between groups were statistically significant. No statistically significant suppressive effects of long-term, low-dose macrolide therapy on the development of pneumonia among older people were found in this small sample. A large-scale, randomized, controlled study is required. Geriatr Gerontol Int 2019; 19: 1006-1009.

Role of combined mucolytic therapy in infectious and inflammatory diseases of the respiratory system in children

The use of combined medicines simultaneously influencing various pathogenetic mechanisms of inflammation and coughing becomes an essential direction of mucoactive therapy in childhood. One of these is thiamphenicol glycinate acetylcysteinate, which has both mucolytic and antibacterial effects, which significantly expands the possibilities of therapy in bacterial etiology of acute and exacerbation of chronic respiratory diseases, increases the effectiveness of therapeutic measures, improves compliance.

Caseworker-assigned discharge plans to prevent hospital readmission for acute exacerbations in children with chronic respiratory illness.

Chronic respiratory conditions are major causes of mortality and morbidity. Children with chronic health conditions have increased morbidity associated with their physical, emotional, and general well-being. Acute respiratory exacerbations (AREs) are common in children with chronic respiratory disease, often requiring admission to hospital. Reducing the frequency of AREs and recurrent hospitalisations is therefore an important goal in the individual and public health management of chronic respiratory illnesses in children. Discharge planning is used to decide what a person needs for transition from one level of care to another and is usually considered in the context of discharge from hospital to the home. Discharge planning from hospital for ongoing management of an illness has historically been referral to a general practitioner or allied health professional or self management by the individual and their family with limited communication between the hospital and patient once discharged. Effective discharge planning can decrease the risk of recurrent AREs requiring medical care. An individual caseworker-assigned discharge plan may further decrease exacerbations. To evaluate the efficacy of individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, in preventing hospitalisation for AREs in children with chronic lung diseases such as asthma and bronchiectasis. We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials registries, and reference lists of articles. The latest searches were undertaken in November 2017. All randomised controlled trials comparing individual caseworker-assigned discharge planning compared to traditional discharge-planning approaches (including self management), and their effectiveness in reducing the subsequent need for emergency care for AREs (hospital admissions, emergency department visits, and/or unscheduled general practitioner visits) in children hospitalised with an acute exacerbation of chronic respiratory disease. We excluded studies that included children with cystic fibrosis. We used standard Cochrane Review methodological approaches. Relevant studies were independently selected in duplicate. Two review authors independently assessed trial quality and extracted data. We contacted the authors of one study for further information. We included four studies involving a total of 773 randomised participants aged between 14 months and 16 years. All four studies involved children with asthma, with the case-planning undertaken by a trained nurse educator. However, the discharge planning/education differed among the studies. We could include data from only two studies (361 children) in the meta-analysis. Two further studies enrolled children in both inpatient and outpatient settings, and one of these studies also included children with acute wheezing illness (no previous asthma diagnosis); the data specific to this review could not be obtained. For the primary outcome of exacerbations requiring hospitalisation, those in the intervention group were significantly less likely to be rehospitalised (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.16 to 0.50) compared to controls. This equates to 189 (95% CI 124 to 236) fewer admissions per 1000 children. No adverse events were reported in any study. In the context of substantial statistical heterogeneity between the two studies, there were no statistically significant effects on emergency department (OR 0.37, 95% CI 0.04 to 3.05) or general practitioner (OR 0.87, 95% CI 0.22 to 3.44) presentations. There were no data on cost-effectiveness, length of stay of subsequent hospitalisations, or adherence to medications. One study reported quality of life, with no significant differences observed between the intervention and control groups.We considered three of the studies to have an unclear risk of bias, primarily due to inadequate description of the blinding of participants and investigators. The fourth study was assessed as at high risk of bias as a single unblinded investigator was used. Using the GRADE system, we assessed the quality of the evidence as moderate for the outcome of hospitalisation and low for the outcomes of emergency department visits and general practitioner consultations. Current evidence suggests that individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, may be beneficial in preventing hospital readmissions for acute exacerbations in children with asthma. There was no clear indication that the intervention reduces emergency department and general practitioner attendances for asthma, and there is an absence of data for children with other chronic respiratory conditions. Given the potential benefit and cost savings to the healthcare sector and families if hospitalisations and outpatient attendances can be reduced, there is a need for further randomised controlled trials encompassing different chronic respiratory illnesses, ethnicity, socio-economic settings, and cost-effectiveness, as well as defining the essential components of a complex intervention.

Amphiregulin potentiates airway inflammation and mucus hypersecretion induced by urban particulate matter via the EGFR-PI3Kα-AKT/ERK pathway

Ambient particulate matter (PM) promotes the development and exacerbation of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma, by increasing inflammation and mucus hypersecretion. However, the biological mechanisms underlying PM-induced airway inflammation and mucus hypersecretion remain unclear. Amphiregulin (AREG) is an important ligand for epidermal growth factor receptor (EGFR) and participates in the regulation of several biological functions. Here, the PM-exposed human bronchial epithelial cell (HBEC) model was used to define the role of AREG in PM-induced inflammation and mucus hypersecretion and its related signaling pathways. The expression of AREG was significantly increased in a dose-dependent manner in HBECs subjected to PM exposure. Moreover, PM could induce inflammation and mucus hypersecretion by upregulating the expression of IL-1α, IL-1β, and Muc-5ac in HBECs. The EGFR, AKT, and ERK signaling pathways were also activated in a time- and dose-dependent manner. The AREG siRNA markedly attenuated PM-induced inflammation and mucus hypersecretion, and activation of the EGFR-AKT/ERK pathway. Exogenous AREG significantly increased the expression of IL-1α, IL-1β, and Muc-5ac, and induced activation of the EGFR-AKT/ERK pathway in HBECs. Further, under PM exposure, exogenous AREG significantly potentiated PM-induced inflammation and mucus hypersecretion, and activation of the EGFR-AKT/ERK pathway. Tumor-necrosis factor-alpha converting enzyme (TACE) and EGFR specific inhibitor pretreatment showed that AREG was secreted by TACE-mediated cleavage to regulate PM-induced inflammation and mucus hypersecretion by binding to the EGFR. Moreover, according to the inhibitory effect of specific inhibitors of the class I PI3K isoforms, AKT and ERK, PM-induced inflammation and mucus hypersecretion was regulated by PI3Kα activation and its downstream AKT and ERK pathways. This study strongly suggests the adverse effect of AREG in PM-induced inflammation and mucus hypersecretion via the EGFR-PI3Kα-AKT/ERK pathway. These findings contribute to a better understanding of the biological mechanisms underlying exacerbation of chronic respiratory diseases induced by PM exposure.