Multidisciplinary Respiratory Medicine最新文献

Background: Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes.

Methods: To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). We compared this global score with the ranking of European countries in terms of death number per million persons.

Results: The ranking of the AAT*air pollution global risk score matched the ranking of the countries in terms of the observed COVID-19 deaths per 1M inhabitants, namely in the case of the first European countries: Belgium, UK, Spain, Italy, Sweden, France. We observed parallelism between the number of COVID deaths and the AAT*air pollution global risk in Europe. AAT anti-protease, immune-modulating and coagulation-modulating activities may explain this finding, although very speculatively.

Conclusions: Even if further studies taking into account genetic background, population density, temporal dynamics of individual epidemics, access to healthcare, social disparities and immunological response to SARS-CoV2 are needed, our preliminary observation urges to open a discussion on gene-environment interactions in COVID-19.

Background: The performance of DPIs depends on several physiological (patient-dependent) and technological (device-dependent) factors. The inspiratory airflow rate is the only active force generated and operating in the system for inducing the required pressure drop and eliciting the resistance-induced turbulence needed to disaggregate the powder through the device. The present study aimed to investigate in the most prevalent respiratory disorders whether and at what extent the inspiratory airflow rate achievable when inhaling through a DPIs' simulator reproducing different intrinsic resistance regimens (low, mid, and high resistance) is affected by peculiar changes in lung function and/or can be predicted by any specific lung function parameter.

Methods: The inspiratory airflow rate was assessed in randomized order by the In-Check DIAL G16 at low, mid, and high resistance regimens in a sample of consecutive subjects at recruitment. Independent predictors of the probability to achieve the expected inhalation airflow rate were investigated by means of a multivariate logistic regression model, specific to the disease.

Results: A total of 114 subjects were recruited (asthmatics n=30; COPD n=50, restrictive patients n=16, and normal subjects n=18). The mean values of the expected inspiratory airflow rate achieved proved significantly different within the groups (p<0.0001), independently of sex and age. In asthmatics and in COPD patients, the mid-resistance regimen proved highly associated with the highest mean values of airflow rates obtained. Low- and high-resistance regimens were significantly less likely to consent to achieve the expected level of inspiratory airflow rate (OR<1 in all comparisons). Restrictive patients performed the lowest airflow rates at the low-resistance regimen (p<0.01). Unlike FEV¹, RV in asthmatics (OR=1.008); RV and I_Raw in COPD (OR=0.587 and OR=0.901, respectively), and FIF and TLC in restrictive patients (OR=1.041, and OR=0.962, respectively) proved the only sensitive predictors of the inspiratory airflow rate achievable at the different resistive regimens.

Conclusions: The intrinsic resistive regimen of DPIs can play a critical role. The patients' lung function profile also affects the extent of their inhalation airflow rate. Some specific lung function parameters (such as: FIF; RV; I_Raw; TLC, but not FEV₁) may be regarded as specific predictors in real-life. In order to optimize the DPI choice, further to the device's technology, also the current patients' lung function should be properly investigated and carefully assessed.

Background: A wide range of mortality rates has been reported in COVID-19 patients on the intensive care unit. We wanted to describe the clinical course and determine the mortality rate in our institution's intensive care units.

Methods: To this end, we performed a retrospective cohort study of 50 COVID-19 patients admitted to the ICU at a large German tertiary university hospital. Clinical features are reported with a focus on ICU interventions, such as mechanical ventilation, prone positioning and extracorporeal organ support. Outcome is presented using a 7-point ordinal scale on day 28 and 60 following ICU admission.

Results: The median age was 64 years, 78% were male. LDH and D-Dimers were elevated, and patients were low on Vitamin D. ARDS incidence was 75%, and 43/50 patients needed invasive ventilation. 22/50 patients intermittently needed prone positioning, and 7/50 required ECMO. The interval from onset of the first symptoms to admission to the hospital and to the ICU was shorter in non-survivors than in survivors. By day 60 after ICU admission, 52% of the patients had been discharged. 60-day mortality rate was 32%; 37% for ventilated patients, and 42% for those requiring both: ventilation and renal replacement therapy.

Conclusions: Early deterioration might be seen as a warning signal for unfavourable outcome. Lung-protective ventilation including prone positioning remain the mainstay of the treatment.

Background: Central obesity is a chronic condition that can contribute to impairments in lung functions. Body position is an important technique that effectively restores and increases lung functions. We aimed to address the possible changes in spirometric parameters in asymptomatic overweight individuals with central obesity with a change in posture from sitting to supine in comparison to normal weight non-obese ones.

Methods: Enrolled subjects were healthy Egyptian males, aged between 20-45 years old, asymptomatic and nonsmokers. They underwent spirometry. The following parameters were measured; forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), FEV₁/FVC ratio, and forced expiratory flow (FEF)25-75%. They were classified into overweight with central obesity (n=40) and healthy control (n=40) groups based on their body mass index (BMI), weight-hip ratio (WHR), and waist circumference (WC). Spirometric parameters were compared between the 2 groups and in both setting and supine positions.

Results: The central obesity group showed significantly lower all spirometric parameters in comparison to the control one. All measured spirometric parameters had a significant reduction with supine position. There were negative correlations between both the WC and WHR and spirometric parameters.

Conclusion: In this study of young Egyptian males, individuals with central obesity had reduced spirometric parameters in comparison to healthy ones. Change in position from sitting to supine has significant effects on spirometric parameters in both healthy middle age males with normal weight and those with overweight and central obesity. These results could have important clinical implications.

Background: The management of severe asthma-associated symptoms is essential since they are distressing to the affected patients, and also greatly impair their quality of life. Dupilumab, a monoclonal antibody, blocks interleukin (IL)-4 and IL-13 signaling, both of which are crucial in acquired and innate immunity pathways through fast signal transduction, leading to an early response to treatment. Although rapid improvement within 1-3 days after dupilumab treatment was observed in moderate-to-severe atopic dermatitis, an early response within 7 days of dupilumab treatment in severe asthma has not been reported.

Methods: Twelve consecutive patients with severe asthma who were newly treated with dupilumab between July 2019 and April 2020 were retrospectively investigated. We evaluated the early response (within 7 days) of patients with severe asthma receiving dupilumab therapy. Asthma control test (ACT) and the daily ACT, which was modified from the ACT to evaluate daily symptoms associated with asthma, were adopted as patient-reported outcomes (PROs) at week 8 and within 7 days, respectively. Patients were stratified into early responders (7 days), late responders (week 8), and non-responders without significant improvement in PROs. Descriptive statistics were adopted due to the limited number of patients.

Results: Four of these 12 patients were early responders, with the following baseline characteristics: body mass index, <25 kg/m²; without depression; baseline forced expiratory volume in 1 second, <1.50 L; and more than one exacerbation in 1 year. On the other hand, five were late responders, and 44.4% of the nine responders were early responders. The higher the eosinophilic count and/or FeNO did not show any relationship between the early responder and nonresponder.

Conclusions: The effect of dupilumab on severe asthma in patients with atopic features could be started earlier than 2 weeks, similar to atopic dermatitis. Daily ACT may be useful in monitoring the early efficacy of dupilumab in treating severe asthma.

Background: Clinical manifestations for pneumonia vary from mild to severe. The PIRO model (predisposition, insult, response, organ dysfunction) was used as scoring system to determine severity of sepsis and pneumonia in adult patients. The PIRO model was modified for sorting the severity of pneumonia in children and predicting its risk of mortality.

Methods: An ambispective cohort study of pneumonia patients aged 1 month to ≤ 18 years admitted over the period from May to September 2020. Data were collected from history, physical examination, laboratory examination, and chest radiography. Based on bivariate analysis (p<0.05 and relative risk (RR) with 95% confidence interval), variables of each PIRO component that were significant for mortality were assigned a value of 1. The cut-off score for predictor of mortality was calculated using the receiver operating characteristics (ROC) curve and the scores were stratified into three degrees of risk based on interquartile range, score ≤Q1 was categorized as low risk; Q1-Q3 was categorized as moderate risk; and score >Q3 was categorized as high risk.

Results: Out of the 80 subjects enrolled, 6 months-5 years was the largest age group (56.3%). The observed mortality was 15/80 (18.8%). The modified PIRO severity score was compiled from significant variables of predisposition (malnutrition), insult (chest radiograph), response (hypoxemia, hypotension, CRP >0.5 mg/dL, PCT >0.5 ng/dL) and organ dysfunction, with range of score 0-7. Score >3 was categorized as a cut-off point score for predictor of mortality with AUC 0.919 (95% CI 0.836-0.968), sensitivity of 80%, and specificity of 84.62%. Subjects with score >3 have RR of 10.544 compared to those with score ≤3. The stratification of score level was low (≤2), moderate (3-4), and high (5-7). The mortality levels were 0%, 46.7%, and 53.3%, respectively.

Conclusions: Modified PIRO severity score can be used as a sorting tool and predictor of mortality risk in children with pneumonia. This score can also be used to select candidates for intensive care, especially in health facilities with limited intensive care capacity.

Background: Transbronchial lung cryobiopsy (TBLC) is a new technique that enables larger tissue collection than can be obtained by conventional transbronchial lung biopsy. TBLC is becoming popular worldwide and is performed for diffuse lung disease and lung cancer. However, only a few reports of TBLC have been published in Japan. This study was performed to evaluate the efficacy and safety of TBLC at our hospital and compare these findings with past reports.

Methods: From April 2018 to January 2020, 38 patients who underwent TBLC for diffuse lung disease at our hospital were evaluated with respect to age, sex, biopsy site, biopsy size, diagnostic disease, and complications.

Results: The patients who underwent TBLC were 20 men and 18 women with an average age of 63.7 years. The average sample size was 5.7 mm, and the diagnostic rate was 65.7% (25/38). Grade ≥2 complications included bleeding (15.8%), pneumothorax (2.6%), and atrial fibrillation (2.6%).

Conclusions: TBLC was considered to be useful for the diagnosis of diffuse lung disease and could be safely performed.