Recurrent Exacerbations Research Articles

A patient-centred, comprehensive model for the care for heart failure: the 360° heart failure centre.

Heart failure (HF) is a chronic heterogeneous clinical syndrome that is unified by the presence of clinical signs and symptoms of congestion and by the difficulty of its diagnosis and management. Its prevalence, of 6.5 million people in the USA,1 is rising due to an increasing incidence and to advances in medical, interventional and device therapies which extend the longevity of the affected patients. Despite these advances, HF is characterised by intermittent and recurrent exacerbations, which are associated with high morbidity, mortality and costs. The estimated costs of HF care are 40 billion dollars annually in the USA, from which >10 billion are due to hospital admissions after presentation to an emergency department (ED).2 Currently, the care paradigm for patients with HF is dichotomous, divided between the care of patients with chronic compensated HF in the outpatient setting and acute decompensated heart failure (ADHF) in an inpatient setting. Patients with compensated HF are managed longitudinally in outpatient clinics, including HF cardiology clinic, general cardiology clinic and primary care clinics. Traditionally, each of these clinics exist as independent ‘silos’ with limited direct communication between them. Furthermore, they are designed, staffed and supplied to provide traditional outpatient care, with limited ability to intervene in a rapid or invasive way. This is clearly focused on the evaluation and management of compensated patients. Perhaps it is not surprising that ADHF accounts for over 1 million annual ED presentations in the USA.2 When a patient with ADHF presents to any of the above-mentioned clinical offices, there is a limited infrastructure and capabilities to address their acute needs. For a mild decompensation, oral diuretics may be adjusted with a plan for follow-up laboratories and phone calls. For a more severe decompensation, a patient may be directly admitted to the hospital or referred to the nearest ED. More …

Interventional Bronchoscopy.

For over 150 years, bronchoscopy, especially flexible bronchoscopy, has been a mainstay for airway inspection, the diagnosis of airway lesions, therapeutic aspiration of airway secretions, and transbronchial biopsy to diagnose parenchymal lung disorders. Its utility for the diagnosis of peripheral pulmonary nodules and therapeutic treatments besides aspiration of airway secretions, however, has been limited. Challenges to the wider use of flexible bronchoscopy have included difficulty in navigating to the lung periphery, the avoidance of vasculature structures when performing diagnostic biopsies, and the ability to biopsy a lesion under direct visualization. The last 10-15 years have seen major advances in thoracic imaging, navigational platforms to direct the bronchoscopist to lung lesions, and the ability to visualize lesions during biopsy. Moreover, multiple new techniques have either become recently available or are currently being investigated to treat a broad range of airway and lung parenchymal diseases, such as asthma, emphysema, and chronic bronchitis, or to alleviate recurrent exacerbations. New bronchoscopic therapies are also being investigated to not only diagnose, but possibly treat, malignant peripheral lung nodules. As a result, flexible bronchoscopy is now able to provide a new and expanding armamentarium of diagnostic and therapeutic tools to treat patients with a variety of lung diseases. This State-of-the-Art review succinctly reviews these techniques and provides clinicians an organized approach to their role in the diagnosis and treatment of a range of lung diseases.

Evaluation and Management of Respiratory Illness in Children With Cerebral Palsy.

Cerebral palsy (CP) is the most common cause of disability in childhood. Respiratory illness is the most common cause of mortality, morbidity, and poor quality of life in the most severely affected children. Respiratory illness is caused by multiple and combined factors. This review describes these factors and discusses assessments and treatments. Oropharyngeal dysphagia causes pulmonary aspiration of food, drink, and saliva. Speech pathology assessments evaluate safety and adequacy of nutritional intake. Management is holistic and may include dental care, and interventions to improve nutritional intake, and ease, and efficiency of feeding. Behavioral, medical, and surgical approaches to drooling aim to reduce salivary aspiration. Gastrointestinal dysfunction, leading to aspiration from reflux, should be assessed objectively, and may be managed by lifestyle changes, medications, or surgical interventions. The motor disorder that defines cerebral palsy may impair fitness, breathing mechanics, effective coughing, and cause scoliosis in individuals with severe impairments; therefore, interventions should maximize physical, musculoskeletal functions. Airway clearance techniques help to clear secretions. Upper airway obstruction may be treated with medications and/or surgery. Malnutrition leads to poor general health and susceptibility to infection, and improved nutritional intake may improve not only respiratory health but also constipation, gastroesophageal reflux, and participation in activities. There is some evidence that children with CP carry pathogenic bacteria. Prophylactic antibiotics may be considered for children with recurrent exacerbations. Uncontrolled seizures place children with CP at risk of respiratory illness by increasing their risk of salivary aspiration; therefore optimal control of epilepsy may reduce respiratory illness. Respiratory illnesses in children with CP are sometimes diagnosed as asthma; a short trial of asthma medications may be considered, but should be discontinued if ineffective. Overall, management of respiratory illness in children with CP is complex and needs well-coordinated multidisciplinary teams who communicate clearly with families. Regular immunizations, including annual influenza vaccination, should be encouraged, as well as good oral hygiene. Treatments should aim to improve quality of life for children and families and reduce burden of care for carers.

Prospective evaluation of vascular changes in acute respiratory infections in children with cystic fibrosis

Background/aim Acute exacerbations and chronic inflammation are risk factors for cardiovascular disease (CVD) in cystic fibrosis (CF) patients. The aim of this study was to investigate the effects of acute exacerbation therapy on arterial stiffness in children with CF.Materials and methods Augmentation index (Aix) and pulse wave velocity (PWV) were measured before and after treatment and 1 month after the end of treatment in patients with acute exacerbation. The relationship between hemodynamic measurements and c-reactive protein (CRP) and pulmonary function tests (PFTs) was investigated.Results Measurements before and after treatment were evaluated in 27 patients and were repeated in 21 patients who were clinically stable 1 month following acute exacerbation. There was a significant decrease in CRP and an increase in spirometry parameters after treatment. While no significant difference was found between PWV (P = 0.33), a significant difference for Aix before (41.95 ± 12.96%) and after (30.95 ± 11.47%) treatment and before treatment and stable clinical condition (34.19 ± 14.36%) was obtained (P =0.00, and P =0.01, respectively). No significant difference in heart rate and other hemodynamic measurements was found. Pretreatment Aix is associated with poor clinical condition (PFTs, BMI, and clinical score) and systemic inflammation (CRP) (P <0.05).Conclusion The decrease of arterial stiffness (Aix) with acute exacerbation treatment in children with CF has been demonstrated. This result shows that systemic inflammation in CF may cause an increase in arterial stiffness and recurrent exacerbations may increase the risk of CVD.

Antineutrophil cytoplasmic autoantibody (ANCA) positive immunoglobulin A (IgA) nephropathy: Case reports and review of literature

BackgroundThere are reports of circulating antineutrophil cytoplasmic autoantibodies (ANCA) in patients with immunoglobulin A (IgA) nephropathy with an uncertain pathogenic role. Aim of the workTo present the findings of myeloperoxidase (MPO) ANCA-positive patients amid a different course of IgA nephropathy with crescents and to discuss the efficacy of immunosuppressive therapy. Case presentationTwo cases of IgA nephropathy associated with positive ANCA are reported and a review of the literature data is presented. The first patient presented with a progressive nephropathy and significantly impaired renal function at baseline, whereas in the second patient renal function remained stable over 10 years, despite the recurrent exacerbations of the disease. Both patients had extrarenal manifestations (joint pain and/or anemia) and elevated markers of inflammation (erythrocyte sedimentation rate, C-reactive protein) that are not typical features for IgA nephropathy. In the first case, immunosuppressive therapy with corticosteroids and cyclophosphamide resulted in improvement of kidney function. The second case showed the potential efficacy of rituximab as an induction remission and maintenance therapy for ANCA-positive IgA nephropathy. ConclusionWhether the association of IgA nephropathy with ANCA positivity is coincidental or constitutes a novel entity remains debated. Circulating ANCA can be found in patients with IgA nephropathy. They can be truly pathogenic and contribute to kidney damage and may induce overt systemic vasculitis or at least extrarenal signs and symptoms. ANCA-positive IgA nephropathy can respond to immunosuppressive regimens, including rituximab, similar to patients with ANCA-associated vasculitis (AAV).

Effects of compound Caoshi silkworm granules on stable COPD patients and their relationship with gut microbiota: A randomized controlled trial.

Patients with chronic obstructive pulmonary disease (COPD) usually experience recurrent acute exacerbations. These patients, especially those with stable COPD, require an effective intervention for treating exacerbations. This study aimed to evaluate the efficacy of Compound Caoshi silkworm granules (CCSGs) in stable COPD patients and to investigate their potential mechanism. A randomized controlled trial was performed at Jinhua Hospital, Zhejiang University. Patients were enrolled in this study if they met the criterion of stable COPD. A total of 40 patients were randomly divided into the following 2 groups: Group A (n = 20, routine treatment (RT) group) and Group B (n = 20, RT plus CCSGs [RT plus CCSGs] group). The duration of treatment was 3 months. Stool samples were collected from all patients on day 0 and the gut microbiota was analyzed using 16s rRNA sequencing. The St. George's Respiratory Questionnaire (SGRQ) scores and lung function were assessed at month 0 and month 3. The components of gut microbiota differed between stable COPD patients and the healthy population. The RT plus CCSGs group showed improved SGRQ scores compared to the RT group. There was no difference in forced expiratory volume-one second, forced vital capacity, and forced expiratory volume-one second/forced vital capacity between the two groups. Furthermore, the abundance of gut microbiota in patients with the top 10 SGRQ scores (Group N) differed from the abundance of gut microbiota in those with the lowest 10 SGRQ scores (Group T). CCSGs have beneficial effects in the improvement of symptoms in stable COPD patients over a 3-month treatment period. The potential underlying mechanism may be attributable to the difference in gut microbiota among patients. However, more research is needed to confirm this conclusion.

PRS57 ASSOCIATION BETWEEN TRANSIENT OPIOID USE AND ACUTE COPD EXACERBATION AMONG OLDER ADULTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Evidence regarding the short-term risk of COPD exacerbation from transient opioid exposure has been found among adult patients under 65 years old, but this relationship has not been evaluated among older adults in the U.S. The objective of this study was to examine the association of transient opioid use and COPD exacerbations among older Medicare beneficiaries with COPD. This study used 5% national Medicare claims data from 2012-2016. A case-crossover design was employed to evaluate the impact of short-term opioid exposure on abrupt COPD exacerbations with each subject serving as their own control. The study population included enrollees in the Medicare fee-for-service program who were diagnosed with COPD and had an acute COPD exacerbation between July 1st, 2012 and December 31st, 2016. The impact of opioid use in the seven days immediately prior to COPD exacerbation was compared to opioid exposure in ten control windows prior to this case window. Adjusted odds ratios (OR) were estimated using conditional logistic regression models to assess the risk of opioid use on COPD exacerbations after controlling for time-varying use of bronchodilators, corticosteroids, benzodiazepines, and β-blockers. Recurrent exacerbation on the same individual was allowed. The robust sandwich estimate for the covariance matrix was utilized to account for the within-subject dependence. A total of 57,542 COPD exacerbation events occurred among the 37,089 beneficiaries who met study inclusion criteria. Opioid exposure in the seven days before an acute COPD exacerbation was significantly associated with the exacerbation (OR: 3.02 [95% CI: 2.94, 3.11]). Transient use of inhaled bronchodilators, methylxanthines, inhaled corticosteroids, systemic corticosteroids, benzodiazepines, and β-blockers were also found to be associated with increased odds of acute COPD exacerbation. Opioids can exacerbate COPD among older adults even when used short-term. Guidelines recommending use of opioids in this population may need to be revisited.

Abstract 302: Factors Influencing Heart Failure Readmissions at the Jesse Brown Veterans Administration Hospital

Background: Heart failure (HF) hospitalizations and readmissions are a major financial burden on patients, caregivers, and the healthcare system. The Jesse Brown Veterans Administration Medical Center (JBVAMC; Chicago, Illinois) has recently been scoring in the 90 th percentile in its HF risk-standardized readmission rate (RSRR) compared to other VA medical centers. Here, we present the factors influencing HF readmission at the JBVAMC. Methods: Veterans discharged from JBVAMC between 7/1/18 and 6/30/19 with a primary diagnosis of HF were identified per ICD-10 codes (I11.0, I13.X, and I50.X). For primary HF discharges between 7/1/18 and 12/31/18, retrospective chart review was performed to assess patient and hospitalization characteristics. Charts were excluded from review if the same veteran’s chart was reviewed for another admission within the preceding 30 days, or if a veteran was discharged against medical advice or to a skilled nursing facility. Continuous variables were analyzed using Student’s t-test and categorical variables with Pearson Chi-Square. Results: Between 7/1/18 and 6/30/19, there were 485 HF discharges resulting in 96 30-day readmissions. Of them, 51 (53%) were due to recurrent HF exacerbation, and 8 (8%) were due to hypotension, dehydration, or acute kidney injury. Only 32% of readmissions (8/25) during the first 7 days after discharge were due to recurrent HF, compared to 70% (19/27) during day 8-14 and 57% (13/23) during day 15-21. In characterizing the index hospitalizations between 7/1/18 and 12/31/18 (N=188), there were 42 (22%) admissions that resulted in readmissions (Table 1). Veterans in this cohort were 72 years old on average, 98% male, and 77% African-American. HF with reduced ejection fraction (HFrEF; EF≤40%) comprised 53% of non-readmitted and 57% of readmitted cohort. Readmitted patients had a higher prevalence of smoking (33% vs 16%, p=0.012) and less likely to have outpatient follow-up within 14 days of discharge (52% vs 29%, p=0.007). There was a low rate of sacubitril/valsartan utilization (N=6) and dietitian consultation (N=7). Conclusion: Over half of our HF readmissions are due to recurrent HF. An emphasis on timely outpatient follow-up after discharge, consideration for sacubitril/valsartan initiation, and dietary education may help reduce our HF readmissions.

COPD exacerbation phenotypes in a real-world five year hospitalisation cohort.

COPD exacerbation phenotypes have been defined in research populations by predominantly infective or inflammatory aetiology. We sought to characterise this in patients admitted to our centre. Case-notes of consecutive patients discharged alive after treatment for acute COPD exacerbations between December 2012 and January 2017 were analysed. Data were collected on treatment, length of stay, C-reactive protein (CRP), eosinophil count and bacterial sputum culture positivity for potentially pathogenic microorganisms (PPM). 1029 exacerbations were included. There was an inverse correlation between CRP and eosinophil count (rho=-0.277, p<0.01). The proportion of eosinophilic exacerbations (eosinophils ≥0.3×109/L) was low (157, 15%). Median length of stay was longer in patients with a CRP >100mg/L (4d [3,8] vs 4d [2,7], p<0.01) or when given antibiotics (4d [2,8] vs 3d [1,6], p<0.001) and shorter if receiving corticosteroids (4d [2,6] vs 6d [3,7], p<0.001). Being sputum culture positive on first exacerbation was associated with sputum culture positivity in subsequent exacerbations. Patients with PPM in sputum culture had a significantly higher median CRP than culture negative patients (38mg/L [18.75, 57] v 18mg/L [8.5,45.5] p<0.05). Length of stay, eosinophil count and CRP were significantly correlated between exacerbation pairs. This real-world population found eosinophilic and high CRP exacerbations to be distinct and significantly stereotyped within individual patients across recurrent exacerbations. High CRP exacerbations are associated with greater healthcare utilisation and chance of sputum positivity with PPM. Eosinophilic exacerbations were associated with lower rate of readmission. Phenotype-driven treatment warrants further investigation in this population.

In patients with an acute asthma exacerbation, does a single intramuscular corticosteroid injection reduce recurrent exacerbations versus five days of oral corticosteroid treatment?

In patients with an acute asthma exacerbation, does a single intramuscular corticosteroid injection reduce recurrent exacerbations versus five days of oral corticosteroid treatment?

Treatment of allergic bronchopulmonary aspergillosis: from evidence to practice.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder caused by dysregulated immune responses against Aspergillus fumigatus. The disorder usually complicates the course of patients with asthma and cystic fibrosis. Patients with ABPA most often present with asthma that is poorly controlled despite inhaled corticosteroids and long-acting β2 agonists. The treatment of ABPA is complicated due to the occurrence of recurrent exacerbations and spontaneous remissions. The drugs used for treating ABPA include systemic glucocorticoids, antifungal agents and biologics, each with its own benefits and drawbacks. In this review, we illustrate the treatment pathway for ABPA in different situations, using a case-based approach. In each case, we present the options for treatment based on the available evidence from recent clinical trials.

Is out-patient based treatment of bronchiectasis exacerbations in children comparable to inpatient based treatment?

Children with bronchiectasis have recurrent exacerbations and may require hospitalization. "Hospital in the home (HITH)" is used as an alternative to hospitalization for children with cystic fibrosis (CF) but to date, there is no published data on children without CF. We describe our experience of HITH (intravenous [IV] antibiotics and at least once-daily physiotherapy-treated airway clearance therapy) in a cohort of children with bronchiectasis, comparing outcomes between hospital and HITH-based pathways. Medical records were retrospectively reviewed in children with bronchiectasis who were hospitalized in our center from July 2016 to July 2018. We compared treatment duration, symptom resolution, adverse events, oral antibiotic prescription on discharge and "time-to-next hospitalization" between children managed with the two treatment pathways. Exacerbations in 63 children (median age = 6 years [range: 1-17]; females = 33, indigenous = 8) with bronchiectasis treated with IV antibiotic therapy were analyzed (HITH n = 45, 71.5%). Duration of treatment and symptom resolution was similar between groups (hospital: median = 14 days [interquartile range {IQR}: 14-14] and 12/18 [66.6%], respectively vs HITH: 14 [14-15.5] and 31/45 [69%]; P = .53 and .85, respectively). There was no significant difference in adverse events (16.6% vs 9%), prescription of oral antibiotics on discharge (44% vs 24%), or "time-to-next hospitalization" (median 42 [IQR: 24-100] vs 67 [IQR: 32-95] weeks) between hospital and HITH groups, respectively. In children with bronchiectasis treated for a severe exacerbation, receiving treatment in the home setting with HITH does not compromise short-term clinical outcomes compared to hospital only treatment. Prospective studies are required to provide more robust evidence in this under-researched area.

A systematic review of methodology used in the development of prediction models for future asthma exacerbation

BackgroundClinical prediction models are widely used to guide medical advice and therapeutic interventions. Asthma is one of the most common chronic diseases globally and is characterised by acute deteriorations. These exacerbations are largely preventable, so there is interest in using clinical prediction models in this area. The objective of this review was to identify studies which have developed such models, determine whether consistent and appropriate methodology was used and whether statistically reliable prognostic models exist.MethodsWe searched online databases MEDLINE (1948 onwards), CINAHL Plus (1937 onwards), The Cochrane Library, Web of Science (1898 onwards) and ClinicalTrials.gov, using index terms relating to asthma and prognosis. Data was extracted and assessment of quality was based on GRADE and an early version of PROBAST (Prediction study Risk of Bias Assessment Tool). A meta-analysis of the discrimination and calibration measures was carried out to determine overall performance across models.ResultsTen unique prognostic models were identified. GRADE identified moderate risk of bias in two of the studies, but more detailed quality assessment via PROBAST highlighted that most models were developed using highly selected and small datasets, incompletely recorded predictors and outcomes, and incomplete methodology. None of the identified models modelled recurrent exacerbations, instead favouring either presence/absence of an event, or time to first or specified event. Preferred methodologies were logistic regression and Cox proportional hazards regression.The overall pooled c-statistic was 0.77 (95% confidence interval 0.73 to 0.80), though individually some models performed no better than chance. The meta-analysis had an I2 value of 99.75% indicating a high amount of heterogeneity between studies. The majority of studies were small and did not include internal or external validation, therefore the individual performance measures are likely to be optimistic.ConclusionsCurrent prognostic models for asthma exacerbations are heterogeneous in methodology, but reported c-statistics suggest a clinically useful model could be created. Studies were consistent in lacking robust validation and in not modelling serial events. Further research is required with respect to incorporating recurrent events, and to externally validate tools in large representative populations to demonstrate the generalizability of published results.

Lessons from "real life experience" of rifaximin use in the management of recurrent hepatic encephalopathy.

BACKGROUNDHepatic encephalopathy (HE) is a major complication of cirrhosis with independent prognostic significance. The current management of HE is mainly based on lactulose. Rifaximin has been shown to decrease the risk of HE recurrence in patients with episodic forms. HE can also be persistent. However, there is no drug support recommendation for rifaximin use in this setting.AIMTo assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE, in “real life conditions”.METHODSIn this retrospective study, using a within-subjects design, we collected data of patients treated with rifaximin for HE in two liver diseases centers, during the six-month period before and during the six-month period after the initiation of rifaximin. The primary effectiveness endpoint was the total number of HE events involving hospitalization.RESULTSRifaximin was introduced for prevention of recurrent HE episodes in 29 out of 62 patients with normal mental status between episodes and for prevention of recurrent acute exacerbations on persistent HE in 33 out of 62 patients. In the “prevention of recurrent HE episodes” group, fewer HE events (0.79 vs 1.78; P = 0.013) were reported during the period of time when rifaximin was used. In the “prevention of recurrent acute exacerbations on persistent HE” group, there was no significant difference in the number of HE-events (1.48 vs 1.77; P = 0.582).CONCLUSIONIn this real-life experience, the effectiveness of rifaximin was confirmed in the prevention of HE episodes recurrence but was not proved in the prevention of acute exacerbations recurrence on persistent HE.

Inhaled Corticosteroids Prescribed for COPD Patients with Mild or Moderate Airflow Limitation: Who Warrants a Trial of Withdrawal?

COPD patients prescribed inhaled corticosteroids (ICS) outside guidelines should be targeted for ICS withdrawal. Within a primary care population of 209,618 we used a combination of digital search algorithm, individual record review, and clinical review to identify COPD patients suitable for a trial of ICS withdrawal. At most, 39% of COPD patients with mild or moderate airflow limitation prescribed ICS were suitable for withdrawal according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Recurrent exacerbations and reversible airway obstruction were the main reasons for patients’ unsuitability for withdrawal. Identifying COPD patients in whom ICS withdrawal should be considered presents a challenge to primary care clinicians.

Low immunoglobulin G4 subclass level is associated with recurrent wheezing in young children.

BackgroundThe most important infectious trigger of asthma is the virus and patients with immunoglobulin deficiencies are prone to recurrent respiratory infections.ObjectiveWe investigated the relationship between immunoglobulin G subclass and recurrent respiratory symptom exacerbation and explored possible therapeutic effects of intravenous immunoglobulin administration.MethodsTwenty-eight infants less than 24 months old with 2 or more recurrent wheezing episodes (infantile wheezer group) and 29 asthmatic children aged 24 months to 15 years (bronchial asthma [B-asthma] group) visited our hospital from October 2010 to January 2018. Serum immunoglobulin G, A, M, E, G1, G2, G3, and G4 were measured in each group and compared. In both groups, serum immunoglobulin and symptoms were compared before and after intravenous immunoglobulin administration.ResultsThe 2 study groups exhibited several statistically significant differences when comparing respiratory virus infection rate (p < 0.001), coinfection rate (p < 0.0001), most commonly found viral infection (human bocavirus vs. human rhinovirus), and immunoglobulin A (p < 0.001), E (p = 0.008), G2 (p < 0.001), and G4 (p = 0.011) levels. In the infantile wheezer group, there was an inverse correlation between immunoglobulin G4 levels and wheezing numbers (R = -0.5538, P = 0.0022). Both groups showed significant changes in immunoglobulin levels and respiratory symptom exacerbations (recurrent wheezing, shortness of breath, chest tightness, cough, and fever) over 1 year after intravenous immunoglobulin administration.ConclusionThere was an association between recurrent wheezing and specific immunoglobulin G deficiencies. We suggest that intravenous immunoglobulin therapy significantly elevates specific immunoglobulin G levels though it lasts only for short term and might be associated with decreased respiratory symptoms. Therefore, low IgG4 levels among infants with recurrent wheezing may be indicative for intravenous immunoglobulin therapy.

КРАЙНЕ РЕДКИЙ СЛУЧАЙ ДВУХСТОРОННЕГО ЭКЗОГЕННОГО РИНОЛИТА 16 ЛЕТНЕЙ ДАВНОСТИ

The article describes a rare case of bilateral rhinolithiasis. The presence of a foreign body in the nasal cavity comprised 16 years. Pathogenetic aspects of the occurrence of the rhinoliths and their chemical composition are presented. Frequent recurrent acute exacerbations of chronic rhinitis, sensations of unpleasant smell, partial loss of smell, breathing problems due to nasal congestion and durable ineffectiveness of previous treatment triggered the patient to address to the clinic. CT revealed the presence of a foreign body on both sides of the nasal cavity. The patient underwent the surgery on bilateral rhinolithiasis with the application of precision technology and optical zoom. The nidus of rhinolith became plastic bullets of a toy gun. Intraoperative complications were not observed. The duration of hospitalization was 5 days. Follow-up evaluation by CT of the nasal cavity and paranasal sinuses in the period of 4 months after surgery revealed the absence of foreign bodies and nasal symptoms. Keywords: Foreign body, bilateral rhinolithiasis, nasal cavity, CT scan.

Integrating Selective Targeted Monoclonal Antibody Therapies for Improved Outcomes in Uncontrolled Asthma

Asthma is one of the most common chronic diseases, with ≤25% of patients experiencing uncontrolled disease.1Patients with uncontrolled, moderate-to-severe asthma are at increased risk of recurrent exacerbations, accelerated decline in lung function, fixed airway obstruction, and have increased utilisation of health care resources.2,3Furthermore, reduced lung function, as assessed by measures such as forced expiratory volume in 1 second (FEV1), is a strong independent predictor of exacerbations, progressive decline in lung function, and all-cause pulmonary and cardiovascular mortality in patients with asthma.2 Achieving asthma control in these patients is therefore critical. The recognition of distinct inflammatory phenotypes within this population has been instrumental in addressing this need. In these patients, there is robust evidence of the pathogenic role of Th2 cytokines, such as IL-4 and IL-13, in the eosinophilic and allergic inflammatory processes.4This in turn has driven the development of targeted biological therapies, particularly selective targeted monoclonal antibodies such as dupilumab which inhibit the biological effects of both IL-4 and IL-13.5 This article reviews four posters displayed at the European Respiratory Society (ERS) International Congress 2019 that presented results demonstrating the efficacy and safety of dupilumab, an anti-IL-4 receptor human monoclonal antibody, compared to placebo for the treatment of uncontrolled, moderate-to-severe asthma, as measured by a range of outcomes.

Vitamin D in the prevention of exacerbations of asthma in preschoolers (DIVA): protocol for a multicentre randomised placebo-controlled triple-blind trial

IntroductionPreschoolers have the highest rate of emergency visits and hospitalisations for asthma exacerbations of all age groups, with most triggered by upper respiratory tract infections (URTIs) and occurring in the...

Oxidative Stress Attenuates TLR3 Responsiveness and Impairs Anti-viral Mechanisms in Bronchial Epithelial Cells From COPD and Asthma Patients.

COPD and asthma exacerbations are commonly triggered by rhinovirus infection. Potentially promoting exacerbations, impaired anti-viral signaling and attenuated viral clearance have been observed in diseased bronchial epithelium. Oxidative stress is a feature of inflammation in asthma and COPD and is prominent during exacerbations. It is not known whether oxidative stress affects the anti-viral signaling capacity. Bronchial epithelial cells from asthmatic and COPD donors were infected with rhinovirus or treated with the oxidative stressor H2O2 followed by exposure to the synthetic viral replication intermediate poly(I:C). Poly(I:C) was used to ascertain a constant infection-like burden. Gene and protein levels of antioxidants as well as anti-viral responses were measured 3 and 24 h post poly(I:C) exposure. Rhinovirus infection and poly(I:C) stimulation induced protein levels of the antioxidants SOD1 and SOD2. In asthmatic bronchial epithelial cells pre-treatment with H2O2 dose-dependently decreased the antioxidant response to poly(I:C), suggesting exaggerated oxidative stress. Further, poly(I:C)-induced IFNβ gene expression was reduced after pre-treatment with H2O2. This epithelial effect was associated with a reduced expression of the pattern recognition receptors RIG-I, MDA5 and TLR3 both on gene and protein level. Pre-treatment with H2O2 did not alter antioxidant responses in COPD bronchial epithelial cells and, more modestly than in asthma, reduced poly(I:C)-induced IFNβ gene expression. Knockdown of TLR3 but not RIG-I/MDA5 abrogated impairment of poly(I:C)-induced IFNβ gene expression by H2O2. We developed a method by which we could demonstrate that oxidative stress impairs anti-viral signaling in bronchial epithelial cells from asthmatic and COPD patients, most pronounced in asthma. The impairment apparently reflects reduced responsiveness of TLR3. These present findings shed light on molecular mechanisms potentially causing reduced interferon responses to rhinovirus infection at exacerbations in asthma and COPD. Together, our findings suggest a possible self-perpetuating vicious cycle underlying recurrent exacerbations, leading to an impaired anti-viral response, which in turn leads to viral-induced exacerbations, causing more airway inflammation.