Obstructive Defect Research Articles

Case Report: Unusual pulmonary involvement in a patient with Costello syndrome

Costello syndrome (CS) is a rare disease with intellectual disability, characterized by failure to thrive, short stature, joint laxity, loose soft skin, and distinctive facial features. This disease is caused by heterozygous germline mutations in the HRAS proto-oncogene. Cardiac and neurological abnormalities are the most common. Cardiovascular manifestations include valvular pulmonary stenosis, arrhythmia and hypertrophic cardiomyopathy. Neurological manifestations are dominated by hydrocephalus, seizures, and tethered spinal cord. Respiratory system manifestations have been reported in people with CS, but a full description of the different lung involvement and respiratory symptoms in these patients is not available. We report the case of a 19-year-old non-smoking man, followed for a Costello syndrome since the age of 8 months, who complained of exertional dyspnea and chest pain for over 18 months. The chest CT scan showed bullous emphysema of the left lung with a giant bulla in the left upper lobe measured than 20 cm long axis responsible for passive atelectasis. Pulmonary function tests revealed a severe non-reversible obstructive ventilatory defect. Faced with the worsening of his dyspnea despite treatment with bronchodilators and recurrent respiratory infections, it was decided to surgically remove the the giant emphysematous bulla. After bullectomy, a clinical and functional respiratory improvement was noted.

Environmental pollutants increase the risks of acute exacerbation in patients with chronic airway disease.

Respiratory infections are a common cause of acute exacerbations in patients with chronic airway disease, however, environmental factors such as air pollution can also contribute to these exacerbations. The study aimed to determine the correlation between pollutant levels and exacerbation risks in areas exposed to environmental pollution sources. From 2015 to 2016, a total of 788 patients with chronic airway diseases were enrolled in a study. Their medical records, including hospital visits due to acute exacerbations of varying severity were analyzed. Additionally, data on daily pollutant levels from the Air Quality Monitoring Network from 2014 to 2016 was also collected and analyzed. Patients with chronic airway disease and poor lung function (FEV1 < 50% or obstructive ventilatory defect) have a higher risk of severe acute exacerbations and are more likely to experience more than two severe acute exacerbations within a year. The study found that in areas exposed to environmental pollution sources, there is a significant correlation between NO2, O3, and humidity with the main causes of severe acute exacerbation. When the levels of NO2 were higher than 16.65 ppb, O3 higher than 35.65 ppb, or humidity higher than 76.95%, the risk of severe acute exacerbation in patients with chronic airway disease increased. Acute exacerbations of chronic airway disease can be triggered by both the underlying disease state and the presence of air pollution. Computer simulations and early warning systems should be developed to predict acute exacerbations of chronic airway disease based on dynamic changes in air pollution.

Risks of obstructive genitourinary birth defects in relation to trihalomethane and haloacetic acid exposures: expanding disinfection byproduct mixtures analyses using relative potency factors.

Some disinfection byproducts (DBPs) are teratogens based on toxicological evidence. Conventional use of predominant DBPs as proxies for complex mixtures may result in decreased ability to detect associations in epidemiological studies. We assessed risks of obstructive genitourinary birth defects (OGDs) in relation to 12 DBP mixtures and 13 individual component DBPs. We designed a nested registry-based case-control study (210 OGD cases; 2100 controls) in Massachusetts towns with complete quarterly 1999-2004 data on four trihalomethanes (THMs) and five haloacetic acids (HAAs). We estimated temporally-weighted average DBP exposures for the first trimester of pregnancy. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for OGD in relation to individual DBPs, unweighted mixtures, and weighted mixtures based on THM/HAA relative potency factors (RPF) from animal toxicology data for full-litter resorption, eye defects, and neural tube defects. We detected elevated aORs for OGDs for the highest of bromodichloromethane (aOR = 1.75; 95% CI: 1.15-2.65), dibromochloromethane (aOR = 1.71; 95% CI: 1.15-2.54), bromodichloroacetic acid (aOR = 1.56; 95%CI: 0.97-2.51), chlorodibromoacetic acid (aOR = 1.97, 95% CI: 1.23-3.15), and tribromoacetic acid (aOR = 1.90; 95%CI: 1.20-3.03). Across unweighted mixture sums, the highest aORs were for the sum of three brominated THMs (aOR = 1.74; 95% CI: 1.15-2.64), the sum of six brominated HAAs (aOR = 1.43; 95% CI: 0.89-2.31), and the sum of nine brominated DBPs (aOR = 1.80; 95% CI: 1.05-3.10). Comparing eight RPF-weighted to unweighted mixtures, the largest aOR differences were for two HAA metrics, which both were higher with RPF weighting; other metrics had reduced or minimally changed ORs in RPF-weighted models.

Association of spirometric restriction with mortality in the silicotics: a cohort study

BackgroundRestrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort.MethodThis retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18–80 years and diagnosed with silicosis during 1981–2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV1/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV1/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV1/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules.ResultsAmong the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44–1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31–1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95–2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18–3.07) than in those with RSP only.ConclusionRSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect.

Frailty in the chronic respiratory patient: association with mortality and clinical features in obstructive, restrictive, and mixed spirometric patterns.

Frailty associates with increased vulnerability to adverse health outcomes and reduced tolerance to medical interventions. Its impact on patients with chronic respiratory diseases, particularly beyond chronic obstructive pulmonary disease (COPD), remains poorly understood. To evaluate the association between frailty index and 5-year mortality across different "spirometric" patterns and the variation in their occurring frailty determinants. This study analyzed data from the SARA study, which enrolled 1968 older adults, to evaluate the association between frailty and 5-year mortality across different spirometric patterns. Frailty was assessed using the frailty index (FI), and spirometry was performed to determine lung function patterns. Hazard ratios (HRs) were calculated using Cox regression models, adjusting for age and sex. Among the study participants, 16% were classified as frail. Frailty was associated with a significantly increased risk of mortality across all spirometric patterns. The 5-year mortality rates were 34.3% in subjects with normal spirometry, 45.1% in those with obstructive defects, 55% in those with restrictive defects, and 42.6% in those with mixed airflow defects. The unadjusted HRs for mortality were 2.64 (95% CI 2.10-3.32) for the overall cohort, 2.24 (95% CI 1.48-3.40) for obstructive defects, 2.45 (95% CI 1.12-5.36) for restrictive defects, and 2.79 (95% CI 1.41-3.17) for mixed airflow defects. After adjusting for age and sex, the HRs remained statistically significant: 2.25 (95% CI 1.37-2.84) for the overall cohort, 2.08 (95% CI 1.37-3.18) for obstructive defects, 2.27 (95% CI 1.04-1.17) for restrictive defects, and 2.21 (95% CI 1.20-3.08) for mixed airflow defects. Frailty is a common syndrome and is associated with a significantly increased risk of mortality. The FI provides valuable information for risk profiling and personalized interventions beyond age and lung function parameters. Including frailty assessment in clinical evaluations can aid in resource allocation and improve patient care in respiratory diseases.

Interventional treatment of outflow tract obstruction and iatrogenic ventricular septal defect after transcatheter aortic valve replacement: a case report

Interventional treatment of outflow tract obstruction and iatrogenic ventricular septal defect after transcatheter aortic valve replacement: a case report

Home noninvasive ventilation use in patients hospitalized with COPD.

The study objective was to estimate the prevalence of chronic hypercapnic respiratory failure (CHRF) and home noninvasive ventilation (NIV) use in a high-risk population, individuals with a history of at least one COPD-related hospitalizations. We retrospectively analyzed electronic medical record data of patients with at least one COPD-related hospitalization between October 1, 2011, and September 30, 2017, to the Iowa City VA Medical Center. We excluded individuals with no obstructive ventilatory defect. Of 186 patients, the overall prevalence of compensated hypercapnic respiratory failure (CompHRF), defined as PaCO2 > 45 mmHg with a pH =7.35-7.45, was 52.7%, while the overall prevalence of home NIV was 4.3%. The prevalence of CompHRF was 43.6% and home NIV was 1.8% in those with one COPD-related hospitalization. Among those with ≥4 COPD-related hospitalizations, the prevalence of CompHRF was 77.8% (14 of 18), and home NIV was 11.1% (2 of 18). Approximately half of individuals with at least one COPD-related hospitalization have CompHRF, but only 8.2% of those use home NIV. Future studies should estimate CHRF rates and the degree of underutilization of home NIV in larger multicenter samples.

Role of Cardiac CTA to Evaluate Branch Pulmonary Artery Stenosis and Ductal Insertion Pattern in Right-Sided Congenital Heart Defects.

There is limited experience in evaluating abnormal ductus arteriosus (DA) insertion pattern by contrast-enhanced cardiac computed tomography (cardiac CT) in patients with right-sided obstructive cardiac defects. Retrospective review of 38 infants with right-sided obstructive cardiac defects who underwent a preoperative cardiac CT between 2016 and 2021. We reviewed the types of cardiac lesions, patterns of ductal insertion, frequency of pulmonary artery (PA) stenosis requiring intervention, total dose length product (DLP), and effective radiation dose. Of 38 infants, 45% were female, the median gestational age and weight were 37 (range 34-40) weeks and 2.95 (range 2-4) kg. The most common pathologies were pulmonary atresia with ventricular septal defect (24%) and tetralogy of Fallot (24%). The abnormal ductal insertion patterns were DA inserting into the left PA in 39%, DA bifurcating into branch PA in 32%, and DA inserting into the right PA in 13%. Of the 38 infants, 76% developed branch PA stenosis requiring intervention. Among patients with abnormal DA insertion, 44% required branch PA arterioplasty during their index surgery compared to 17% without abnormal DA insertion. Regardless of the type of abnormal DA insertion, 67% developed bilateral branch PA stenosis over time. The mean DLP was 8mGy-cm and the mean calculated effective radiation dose was 0.312mSv. The utilization of contrast-enhanced cardiac CT in infants with right-sided obstructive heart defects can offer crucial insights into abnormal ductus arteriosus insertion patterns. This information is valuable for effective procedure planning and for monitoring the development of branch pulmonary artery stenosis.

Coexistence of pulmonary actinomycosis with diffuse panbronchiolitis: A case report

Abstract Pulmonary actinomycosis is difficult to diagnose, and many clinicians lack an understanding of the disease. Delayed diagnosis and misdiagnosis are common. Diffuse panbronchiolitis (DPB) is a rare clinical and pathologic syndrome that involves pulmonary bronchiolitis and chronic sinusitis. This report describes a case of DPB complicated with pulmonary actinomycosis. A 77-year-old Chinese male was admitted with complaints of chronic cough, expectoration, shortness of breath, and fever. He had a history of smoking, drinking, and dental caries. Chest examination revealed coarse crackles. Pulmonary function tests showed an obstructive defect. Computed tomography of the chest showed consolidation shadows, thickening and dilatation of bronchiolar walls, and diffuse central lobular nodules in both lungs. Histopathological examination of a surgical lung biopsy specimen confirmed DPB combined with actinomycosis. The patient’s symptoms and radiological findings were significantly improved after penicillin combined with azithromycin therapy. Actinomycosis should be considered in older men who have structural lung diseases with recurrent lung infections. Early histological diagnosis and combination antibiotic therapy are very important in such patients.

The Diagnostic Accuracy of Electrocardiogram in Differentiating Takotsubo Cardiomyopathy in Patients Presenting as Anterior Wall St-Segment Elevation Myocardial Infarction and Taking Coronary Angiography as Gold Standard

Myocardial infarction: Myocardial infarction is the irreparable damage to heart muscles resulting in necrosis &amp; is the leading cause of death; resulting in 500,000-700,000 important deaths related to the coronary artery occur each year. Cardiovascular disease is the most common reason resulting in premature mortality as well as morbidity among various ethnic group of white, black and Hispanic populations. Takotsubo Cardiomyopathy: TCM is a condition that affects the heart reversible syndrome, characteristic of decrease(hypokinesia)/ near absent movement (akinesia) of distal half of interventricular septum &amp; cardiac apex showed as apical ballooning on echocardiogram with absence of an obstructive defect in epicardial coronary arteries following an emotional disturbance. Objective: To determine the diagnostic accuracy of electrocardiographic findings (elevation &lt; 1mm Takotsubo cardiomyopathy can be identified in lead V1 in patients who have anterior wall ST-segment elevation myocardial infarction by taking coronary angiography as gold standard. Design: Cross-sectional survey Subjects &amp; Methods: Using 250 incidences in the sample, and a 95% confidence level, a 13% error margin, and the anticipated percentage of Takotsubo cardiomyopathy i.e, 18% by using 74.2% sensitivity and 80.6% specificity of electrocardiographic findings i.e, ST-elevation of &gt; 1mm in V1 in the detection of Takotsubo cardiomyopathy when myocardial infarction with ST-elevation in the anterior wall is the presenting symptom and coronary angiography as gold standard2. Results: The patients were 49 + 13 years old on average. Sensitivity &amp; specificity of ECG criteria were 40.78% &amp; 78.65%. The positive &amp; negative predictive values were 43.28% &amp; 76.5% respectively. Practical Implication: Our study showed negative association of ST-elevation of &gt;1mm in ECG lead V1 to differentiate TC from anterior wall myocardial infarction. Further studies should be done to probe into the diagnostic accuracy of ECG in differentiating TC from acute anterior wall myocardial infarction. Conclusion: Electrocardiography is not diagnostic for distinguishing acute anterior wall pain from Takotsubo cardiomyopathy myocardial infarction so additional investigations need to be performed to diagnose the Takotsubo Cardiomyopathy. Keywords: Myocardial infarction, Takotsubo cardiomyopathy, Electrocardiogram, diagnostic accuracy Coronary angiography.

Relevance of serum levels of the endoplasmic reticulum stress protein GRP78 (glucose-regulated protein 78 kDa) as biomarker in pulmonary diseases

Cellular stress and inflammation contribute to the initiation and progression of a variety of pulmonary diseases. Endoplasmic reticulum (ER) stress and its main regulator GRP78 (glucose-regulated protein 78 kDa) appear to be involved in the pathogenesis of pulmonary diseases, and GRP78 was found to be a biomarker in a wide range of inflammatory diseases. The aim of this study was to investigate the relevance of serum GRP78 in pulmonary disorders.In this prospective cohort study, 78 consecutive patients with chronic obstructive pulmonary disease (COPD, n = 28), asthma (n = 38) or interstitial lung disease (ILD, n = 12) underwent measurement of serum GRP78 levels by ELISA.The mean age of patients was 59.8 ± 12.4 years, 48.7% were female. Patients with elevated GRP78 levels (> median) offered a significantly better oxygenation status (capillary pO2: 75.3 ± 11.7 mmHg vs. 67.8 ± 15.9 mmHg, p = 0.02). Significant correlations were observed between GRP78, on the one hand, and haemoglobin, high-sensitivity C-reactive protein (hs-CRP) and eosinophil counts, on the other hand (haemoglobin: Pearson’s r = −0.25, hs-CRP: r = 0.30, eosinophils: r = 0.63).Subsequently, we evaluated GRP78 measurements in function of severity stratifiers of the specific underlying pulmonary disease. ILD patients with a severe diffusion impairment (DLCO< 40% of predicted), exhibited a significant decrease in GRP78 levels (p = 0.01). In COPD and asthma, both characterized by obstructive ventilatory defects, a forced expiratory volume in one second (FEV1) <30% of predicted was accompanied by significantly lower GRP78 (p = 0.0075).In both obstructive and restrictive pulmonary disorders, GRP78 protein concentrations were reduced with increasing disease severity. These data suggest a prevalent role of GRP78 in the presently studied pulmonary disorders.

Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery.

Respiratory muscle activity is increased in patients with chronic respiratory disease. 18 F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value? Patients undergoing 18 F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort. One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51-2.25], sternocleidomastoid 1.64 [1.34-1.95], intercostal 1.01 [0.84-1.16], diaphragm 1.79 [1.41-2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r=-0.29, p < 0.001) and SCM (r=-0.17, p=0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r=0.17, p=0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO2 max (15.4 [14.2-17.5] vs. 17.2 mL/kg/min [15.2-21.1], p=0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01). Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. 18 F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.

Nocturnal continuous positive airway pressure offers symptomatic benefit in excessive dynamic airway collapse despite normal sleep study.

Excessive dynamic airway collapse (EDAC) and tracheobronchomalacia (TBM) cause debilitating symptoms yet are often misdiagnosed as asthma or chronic obstructive pulmonary disease (COPD). EDAC/TBM should be considered in all cases of obstructive ventilatory defect refractory to medical management. Diagnosis is made with flexible bronchoscopy and/or inspiratory and expiratory phase computed tomography (CT) scans. Treatment should be individualised and "pneumatic stenting" with the use of continuous positive airway pressure (CPAP) may lead to symptomatic relief, and in some cases regardless of the degree of collapse or absence of sleep disordered breathing in overnight oximetry. The case of a 63-year-old female referred to a tertiary respiratory department for a trial of CPAP due to EDAC is presented. Over the course of a few months, she had presented frequently to hospital with cough and shortness of breath which had been attributed to asthma. As she had not responded to treatment, an inpatient flexible bronchoscopy was performed which identified EDAC of the right main bronchus and she was referred to a tertiary ventilation department. Despite a normal sleep study whilst self-ventilating, nocturnal CPAP therapy significantly improved quality and duration of sleep, daytime symptoms and therefore quality of life. She was discharged with nocturnal CPAP and remains adherent to treatment.

Morphological Characteristics and Pulmonary Function of Naval Saboteurs and Ground Special Forces of the Armed Forces of Montenegro

The results of numerous medical and kinesiological studies indicate the existence of differences in pulmonary function in relation to age, body height, and the relationship between certain parameters of body composition. The aim of this study was to determine the state of morphological characteristics and pulmonary function of naval saboteurs and ground Special Forces of the Armed Forces of Montenegro. The sample of participants included 30 naval saboteurs aged 30.3±6 years and 30 members of the ground special forces aged 25.6±5 years. The sample of measuring instruments included 4 indicators each for the evaluation of longitudinal dimensionality, transversal dimensionality, mass and body volume, subcutaneous fat, body composition, and pulmonary function. The central and dispersion parameters of the variables were calculated. The specificities of body composition of the naval saboteurs and members of the ground Special Forces of the AF of Montenegro were determined, while the parameters of lung volume and capacity and the parameters of airway flow indicated an excellent state of their respiratory function. Furthermore, it was determined that the studied members of the armed forces had no individual health risks in the sense of the onset of obesity or obstructive ventilatory defects. The results obtained indicate the need for further studies which would predominantly focus on the impact of individual morphological measurements and parameters of body composition on pulmonary function. This would provide important data both for the armed forces in the sense of improving the training system and the realization of specific tasks, as well as for kinesiology as a science from the aspect of determining certain regularities in the functioning of the human body in specific living and working conditions in the armed forces.

Impact of preheart transplant spirometry and DLCO measurement on post-transplant pulmonary outcomes

Pulmonary function tests (PFT) are a frequent component of heart transplant evaluation. In cardiac surgery abnormal PFTs, especially reduced DLCO, have been associated with poor outcomes. We sought to evaluate the impact of pretransplant PFTs on post-transplant pulmonary outcomes and patient survival. Among the 652 adult heart transplant recipients between January 1, 2010 and July 31, 2021, 462 had PFTs and constituted the patient cohort. Obstructive ventilatory defects (OVD), restrictive ventilatory defects (RVD), and reduced DLCO were defined according to established criteria. The primary outcome was the combined endpoint of a post-transplant pulmonary complication defined as reintubation, postoperative pneumonia, prolonged intubation, or tracheostomy. Secondary outcomes included 90-day all-cause mortality, length of stay, and the odds of individual pulmonary complications. Kaplan-Meier survival analysis, multivariable Cox proportional-hazards regression, and multivariable logistic regression were performed to compare outcomes between the groups. Patients with severe OVD (OR 1.48, 95% CI 1.18-5.23, p=0.02) or severely reduced DLCO (OR 1.95, 95% CI 1.19-3.20, p=0.008) had increased odds of post-transplant pulmonary complications. Following multivariable adjustment, severe OVD (aOR 2.67, 95% CI 1.15-6.19, p=0.02) and severely reduced DLCO (aOR 1.79, 95% CI 1.05-3.04) remained strongly associated with post-transplant pulmonary complications. Patients with any degree of extrinsic RVD, moderate or less OVD, or moderately reduced DLCO or less did not have increased odds of post-transplant pulmonary complications. Ninety-day post-transplant survival was significantly reduced for both severe OVD (97.2% vs 86.5%, p=0.04) and severely reduced DLCO (97.3% vs 90.4%, p=0.004). Post-transplant ICU and hospital length of stay were nominally longer for both groups as well. Severe OVD or severely reduced DLCO on preheart transplant PFTs were associated with increased odds of post-transplant pulmonary complications and early mortality.

Assessment of pulmonary function of post-COVID-19 patients of a tertiary hospital at three months following discharge

In this cross-sectional study from October 2020 to September 2021, pulmonary function was assessed in 40 (24 severe and 16 non-severe) post- COVID-19 patients at three months following hospital discharge by convenient sampling in post-COVID follow-up clinic at Department of Respiratory Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka. Among 40 subjects, 17 (42.5%) had restrictive defect, 1 (2.5%) had obstructive defect and 22 (55%) had normal spirometry. There was reduced total lung capacity (TLC) in 17 (42.5%) subjects and reduced diffusing lung capacity for carbon monoxide (DLCO) in 20 (50%) subjects. Mean six minutes walking distance (6MWD) was low (387.6±99.4 meters). Oxygen desaturation was in 4 (10%) cases. Frequency of restrictive defect was higher in severe than non-severe subjects (54.2% vs. 25%). Reduced TLC was in 62.5% of severe and 12.5% of non-severe cases. There was higher frequency of reduced DLCO in severe than non-severe casese (62.5% vs. 31.3%). 6MWD was lower in severe than non-severe group (354.0±134.9 vs. 438.2±51.4 meters, P=0.02). Pulmonary function was found significantly impaired in post-COVID patients which was more prominent in severe disease group. BSMMU J 2022; 15(3): 192-196

Genetic aetiology distribution of 398 foetuses with congenital heart disease in the prenatal setting.

Copy number variant-sequencing (CNV-seq) and exome sequencing (ES) have been used as powerful tools in understanding the role of genetic variants in congenital heart diseases (CHDs). A few previous large cohort studies have utilized CNV-seq and ES to investigate prenatally diagnosed CHD. Here, we sought to determine the value of CNV-seq and ES for genetic evaluation of foetal CHDs. We recruited 398 pregnant women diagnosed with CHDs between 8 January 2017 and 30 November 2020. CNV-seq and ES were performed on foetal and parent samples. CHD cases were classified following the guidelines of the International Paediatric and Congenital Cardiac Code and the Tenth and Eleventh Revisions of the International Classification of Diseases. Data on aneuploids (AUP), pathogenic CNVs (pCNVs), and single nucleotide variants (SNVs) were collected and compared, following appropriate procedures. We identified genetic abnormalities in 129 (32.41%) foetuses. These abnormalities included AUP (10.80%), pCNVs (13.32%), and SNVs (8.04%). ES analysis yielded higher SNVs in cases without AUP or pCNVs. Non-isolated CHDs were associated with higher genetic abnormalities than isolated CHDs, mainly due to AUP differences between the two groups. The prevalence of genetic defects was the highest in foetuses with atrioventricular septal defects (AVSD), left ventricular outflow tract obstruction (LVOTO), and conotruncal defects (CTD). AVSD and anomalies of atrioventricular junctions and valves were associated with AUP abnormalities. CTD, anomalies of extrapericardial arterial trunks, and anomalies of the ventricular outflow tracts were the most common CHD categories diagnosed using CNVs. The most common CHDs associated with single ventricle (SV) abnormalities were heterotaxy (Hex) (14.89%), LVOTO (14.58%), and ventricular septal defect (VSD) (26.67%, 4/15). Although the ES yields were higher than CNV-seq for VSD (44.4%, 4/9), LVOTO (20%, 7/35), Hex (14.89%, 7/47), and CTD (9.1%, 11/121), its diagnostic yield did not increase for SV (6.7%, 1/15), AVSD (3.8%, 1/26), or right ventricular obstruction defects (2.6%, 1/38). The most common mutations were observed in KMT2D, CHD7, and NOTCH1. To our knowledge, this is the largest cohort study to investigate the incidence of SNVs using ES in foetal CHD. CNV-seq and ES identified genetic abnormalities in nearly 1/3 of foetal CHD cases. Thus, CNV-seq and ES can provide clinically relevant information for pregnancy management.

Delayed lung function testing after COVID-19 to detect persistent lung function abnormalities - The DELTA - COVID-19 lung function study.

Coronavirus disease 2019 (COVID-19) has made its presence felt as the worst pandemic witnessed till date in the 21st century. The mortality and morbidity associated with COVID-19 does not end with the acute pneumonia and respiratory failure and consequences extend well into the subsequent weeks to months in a minority. After recovery from severe disease, symptoms, lung function abnormalities and radiological changes are known to persist for varying length of time in a small proportion of patients. Various studies report different incidences of lung function abnormalities post-COVID-19. The present study describes the occurrence, severity, pattern and risk factors for persistent lung function abnormalities post-COVID-19 patients. The present study was aimed to find out the occurrence of persistent lung function abnormalities in patients hospitalised with COVID-19 at three months of discharge who had normal previous lung function prior to COVID-19. In those with persisting abnormal lung function, the severity, pattern and risk factors for persistent lung function abnormalities were also studied. The present study was a retrospective study in patients hospitalised with COVID-19 who had radiological evidence of pneumonia at admission. Patients with prior abnormal lung function were excluded from the study. Lung function was analysed with spirometry, 6-min walk test and diffusion capacity between day 85 and 95 of hospital discharge and the occurrence, severity and pattern of impairment was described. Lung function impairment was correlated with baseline characteristics and univariate regression analysis was done to identify risk factors for persisting functional impairment. 39 patients were included in the study. Spirometry at follow up showed a restrictive ventilatory defect in 26 out of 39 patients (64%) and a normal study was noted in 12 patients. One patient had an obstructive ventilatory defect. Diffusion impairment was present in 27 patients and normal transfer factor was seen in 12 patients. The degree of diffusion impairment was mild in 16 patients and moderate in 11 patients. Univariate regression analysis revealed that age, history of systemic hypertension, severe hypoxia at presentation, and extent of lung involvement by CT chest were associated with lung function impairment. Almost two-thirds of patients hospitalised with COVID-19 pneumonia have persistent lung function abnormalities at three months post-discharge. Advanced age, severe disease and medical comorbidities increase the risk of persistent functional abnormalities.

PARADOXICAL BRONCHOSPASM IN A SARCOIDOSIS COHORT AT A TERTIARY MEDICAL CENTER

PARADOXICAL BRONCHOSPASM IN A SARCOIDOSIS COHORT AT A TERTIARY MEDICAL CENTER

Genetic abnormalities in fetal congenital heart disease with aberrant right subclavian artery

Fetal aberrant right subclavian artery (ARSA) is a relatively common sonographic finding. Congenital heart disease (CHD) is the most common structural abnormality in patients with ARSA. We aimed to assess the prevalence of genetic abnormalities, particularly sequence variants, in fetuses with CHD and ARSA. By clinical phenotyping and genomic sequencing, we retrospectively reviewed all fetuses with a prenatal diagnosis of CHD combined with ARSA at a single center. As a result, we identified 30 fetuses with ARSA combined with CHD, with conotruncal anomalies being the most common (n = 12, 40%), followed by left ventricular outflow tract obstruction (n = 6, 20%) and atrioventricular septal defects (n = 6, 20%). Overall, 18 (60%) cases had a genetic diagnosis. Copy number variation sequencing analysis identified six (20%) fetuses with aneuploidy and seven (23%) with pathogenic copy-number variants. Whole-exome sequencing (WES) analysis of the remaining 17 cases revealed diagnostic genetic variants in five (29%) cases, indicating that the diagnostic yield of WES for the entire cohort was 17% (5/30). Our findings reveal the high burden of genetic abnormalities in fetal CHD with ARSA. Single-gene disorders contribute substantially to the genetic etiology of fetal CHD with ARSA.