Chronic Respiratory Symptoms Research Articles

Respiratory Phenotypes for Preterm Infants, Children, and Adults: Bronchopulmonary Dysplasia and More.

Ongoing advancements in neonatal care since the late 1980s have led to increased numbers of premature infants surviving well beyond the neonatal period. As a result of increased survival, many individuals born preterm manifest chronic respiratory symptoms throughout infancy, childhood, and adult life. The archetypical respiratory disease of prematurity, bronchopulmonary dysplasia, is the second most common chronic pediatric respiratory disease after asthma. However, there are several commonly held misconceptions. These misconceptions include that bronchopulmonary dysplasia is rare, that bronchopulmonary dysplasia resolves within the first few years of life, and that bronchopulmonary dysplasia does not impact respiratory health in adult life. This focused review describes a spectrum of respiratory conditions that individuals born prematurely may experience throughout their lifespan. Specifically, this review provides quantitative estimates of the number of individuals with alveolar, airway, and vascular phenotypes associated with bronchopulmonary dysplasia, as well as non-bronchopulmonary dysplasia respiratory phenotypes such as airway malacia, obstructive sleep apnea, and control of breathing issues. Furthermore, this review illustrates what is known about the potential for progression and/or lack of resolution of these respiratory phenotypes in childhood and adult life. Recognizing the spectrum of respiratory phenotypes associated with individuals born preterm and providing comprehensive and personalized care to these individuals may help to modulate adverse respiratory outcomes in later life.

Determinants of Chronic Respiratory Symptoms among Pharmaceutical Factory Workers.

Background Chronic respiratory symptoms including chronic cough, chronic phlegm, wheezing, shortness of breath, and chest pain are manifestations of respiratory problems which are mainly evolved as a result of occupational exposures. This study aims to assess determinants of chronic respiratory symptoms among pharmaceutical factory workers. Methods A case control study was carried out among 453 pharmaceutical factory workers with 151 cases and 302 controls. Data was collected using pretested and structured questionnaire. The data was analyzed using descriptive statistics and bivariate and multivariate analysis. Result Previous history of chronic respiratory diseases (AOR = 3.36, 95% CI = 1.85–6.12), family history of chronic respiratory diseases (AOR = 2.55, 95% CI = 1.51–4.32), previous dusty working environment (AOR = 2.26, 95% CI = 1.07–4.78), ever smoking (AOR = 3.66, 95% CI = 1.05–12.72), and service years (AOR = 1.86, 95% CI = 1.16–2.99) showed statistically significant association with chronic respiratory symptoms. Conclusion Previous history of respiratory diseases, family history of chronic respiratory diseases, previous dusty working environment, smoking, and service years were determinants of chronic respiratory symptoms. Public health endeavors to prevent the burden of chronic respiratory symptoms among pharmaceutical factory workers should target the reduction of adverse workplace exposures and discouragement of smoking.

High Prevalence of Chronic Respiratory Symptoms among Autorickshaw Drivers of Urban Puducherry, South India.

Context:Auto-rickshaw (three wheelers open cabin type of vehicle) drivers are exposed to traffic air pollution. Studies have demonstrated reduced pulmonary function among drivers. However, limited studies have determined the prevalence of chronic respiratory symptoms or chronic obstructive pulmonary disease (COPD) among drivers.Aims:Among auto-rickshaw drivers of urban Puducherry to determine prevalence of (i) chronic respiratory symptoms by using Indian Study on Epidemiology of Asthma, Respiratory Symptoms, and Chronic Bronchitis (INSEARCH) questionnaire and (ii) COPD by measuring peak expiratory flow rate (PEFR).Setting and Designs:Cross-sectional, descriptive study.Subjects and Methods:Cluster random sampling was used to select 297 auto-rickshaw drivers. Subjects were interviewed using the INSEARCH questionnaire. PEFR was measured using Wright's peak flow meter. We also assessed exposure to tobacco smoke.Statistical Analysis Used:Prevalence and 95% confidence interval of chronic respiratory symptoms and COPD were calculated.Results:All the auto-rickshaw drivers were male, and 75% were in the age group of 31–50 years. They spend most of the time on the roadside either driving or waiting at the auto-stand. Prevalence of nonspecific respiratory symptoms among auto-rickshaw drivers was 76% (breathlessness on exertion 68%, cough at night and phlegm in the morning 22%, wheezing 18% assessed for last 12 months). Around 28% of them had PEFR <80%. The prevalence of tobacco smoking was also high (64%), and 100% had exposure to tobacco smoke at the workplace.Conclusion:The nonspecific chronic symptoms were high among auto-rickshaw drivers as compared to the general population noted from a multicentric study done in India. We recommend that auto-rickshaw drivers should use personal protective equipment and would require regular screening and treatment for respiratory impairment.

Rarely occurrance of two diffuse idiopathic neuroendocrine cell hyperplasia cases

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disease which needs a long time for diagnosis and usually defined by case reports and small series. We reported two cases, one with 67 and the other with 66-years-old, both of them were female. They presented with long-lasting complaints of cough and shortness of breath. Computed tomography of patients showed multiple nodules on the basis of lungs, and additionally, mosaic perfusion was seen in the first case. Tissue samples were taken with video-assisted thoracic surgery, and the patients were diagnosed with DIPNECH by immunohistochemical examination. We wanted to emphasize the importance of DIPNECH which is a rare clinical entity causing chronic respiratory symptoms which should be considered in differential diagnosis of multiple pulmonary nodules.

Community prevalence of chronic respiratory symptoms in rural Malawi: Implications for policy.

BackgroundNo community prevalence studies have been done on chronic respiratory symptoms of cough, wheezing and shortness of breath in adult rural populations in Malawi. Case detection rates of tuberculosis (TB) and chronic airways disease are low in resource-poor primary health care facilities.ObjectiveTo understand the prevalence of chronic respiratory symptoms and recorded diagnoses of TB in rural Malawian adults in order to improve case detection and management of these diseases.MethodsA population proportional, cross-sectional study was conducted to determine the proportion of the population with chronic respiratory symptoms that had a diagnosis of tuberculosis or chronic airways disease in two rural communities in Malawi. Households were randomly selected using Google Earth Pro software. Smart phones loaded with Open Data Kit Essential software were used for data collection. Interviews were conducted with 15795 people aged 15 years and above to enquire about symptoms of chronic cough, wheeze and shortness of breath.ResultsOverall 3554 (22.5%) participants reported at least one of these respiratory symptoms. Cough was reported by 2933, of whom 1623 (55.3%) reported cough only and 1310 (44.7%) combined with wheeze and/or shortness of breath. Only 4.6% (164/3554) of participants with chronic respiratory symptoms had one or more of the following diagnoses in their health passports (patient held medical records): TB, asthma, bronchitis and chronic obstructive pulmonary disease)ConclusionsThe high prevalence of chronic respiratory symptoms coupled with limited recorded diagnoses in patient-held medical records in these rural communities suggests a high chronic respiratory disease burden and unmet health need.

Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial

Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FeNO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms. In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1:1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 μg, two puffs twice per day, equivalent to 800 μg per day beclomethasone dipropionate) or placebo. Randomisation was stratified by baseline FeNO measurement: normal (≤25 parts per billion [ppb]), intermediate (>25 tp <40 ppb), and high (≥40 ppb). The primary endpoint was change in Asthma Control Questionnaire (ACQ7) mean score. We used generalised linear modelling to assess FeNO as a predictor of response, estimating an interaction effect between FeNO and treatment on change in ACQ7. We did our primary and secondary analyses in the per-protocol set, which excluded patients with non-completion of the primary endpoint, non-compliance to treatment (ascertained by patient report), and study visits made outside the predefined visit windows. This study is registered on ClinicalTrials.gov, number NCT02294279. Between Feb 4, 2015, and July 12, 2016, we randomly assigned 294 patients to extrafine inhaled corticosteroid treatment (n=148) or placebo (n=146). Following exclusions due to protocol violations, we analysed 214 patients (114 extrafine inhaled corticosteroids and 100 placebo). We observed a significant interaction between baseline FeNO and treatment group for every 10 ppb increase in baseline FeNO, with the change in ACQ7 greater in the extrafine inhaled corticosteroids group than in the placebo group (difference between groups 0·071, 95% CI 0·002 to 0·139; p=0·044). The most common adverse events were nasopharyngitis (18 [12%] patients in the treatment group vs 13 [9%] in the placebo group), infections and infestations (25 [17%] vs 21 [14%]), and respiratory, thoracic, and mediastinal disorders (13 [9%] vs 17 [12%]). FeNO measurement is an easy and non-invasive tool to use in clinical practice in patients with non-specific respiratory symptoms to predict response to inhaled corticosteroids. Further research is needed to examine its role in patients with evidence of other airway diseases, such as chronic obstructive pulmonary disease. Sponsored by OPRI with partial funding by Circassia and study drugs provided by TEVA.

Associations between vitamin D, adiposity, and respiratory symptoms in chronic spinal cord injury

Context/ObjectivePersons with chronic spinal cord injury (SCI) have an increased risk of respiratory-related morbidity and mortality and chronic respiratory symptoms are clinical markers of future respiratory disease. Therefore, we sought to assess potentially modifiable factors associated with respiratory symptoms, with a focus on circulating vitamin D and measures of body fat.DesignCross-sectional study.SettingVeterans Affairs Medical Center.ParticipantsThree hundred forty-three participants (282 men and 61 women) with chronic SCI participating in an epidemiologic study to assess factors influencing respiratory health recruited from VA Boston and the community.MethodsParticipants provided a blood sample, completed a respiratory health questionnaire, and underwent dual x-ray absorptiometry (DXA) to assess % body fat. Logistic regression was used to assess cross-sectional associations between respiratory symptoms and plasma vitamin D and measures of body fat with adjustment for a number of potential confounders.Outcome MeasuresChronic cough, chronic phlegm, any wheeze, persistent wheeze.ResultsAfter adjustment for a number of confounders (including smoking), participants with greater %-android, gynoid, trunk, or total body fat had increased odds ratios for any wheeze and suggestive associations with persistent wheeze, but not with chronic cough or phlegm. Vitamin D levels were not associated with any of the respiratory symptoms.ConclusionIncreased body fat, but not vitamin D, was associated with wheeze in chronic SCI independent of a number of covariates.

Long-term Pulmonary Outcomes in Pediatric Survivors of High-risk Neuroblastoma.

Children with high-risk neuroblastoma are exposed to multimodality therapies early in life and survivors confront late therapy-related toxicities. This study assessed respiratory symptoms, pulmonary function tests (PFTs), and risk factors for abnormalities among survivors. High-risk neuroblastoma survivors followed in the long-term follow-up clinic at Memorial Sloan Kettering Cancer Center were enrolled. Self-administered symptom questionnaires were completed. Medical records were reviewed for treatment information and comorbidities. PFTs included spirometry, plethysmography, and diffusion capacity of the lung for carbon monoxide (DLCO). Thirty-nine survivors participated (median age at study: 11.4 y; median age at diagnosis: 2.3 y; median time since completion of therapy: 5.5 y). Chronic respiratory symptoms were reported for 33%. PFT abnormalities were identified in 79% and included low forced expiratory volume in 1 second (38%), decreased total lung capacity (44%), and abnormal DLCO (67%). PFT abnormalities were mostly mild to moderate. Mean forced vital capacity, forced expiratory volume in 1 second, and total lung capacity were normal and mean DLCO was mildly abnormal. Risks included thoracic surgery, chest radiation therapy, thoracic surgery plus chest radiation therapy, and shorter time since completion of therapy (P<0.05). Although respiratory abnormalities were common, they were mostly mild or moderate. Continued pulmonary surveillance of this at-risk population is warranted.

C-Reactive Protein Concentrations Among Crop and Dairy Farmers with Stable Chronic Obstructive Pulmonary Disease.

AIM:To assess the mean serum C-reactive protein concentrations among farmers and office controls, and further examined its relation to exposure duration, smoking habit, as well as presence or absence of COPD.METHODS:A cross-sectional survey was performed including examined group (EG), composed of agricultural workers (87 crop - EG1 and 83 dairy farmers - EG2), and control group (CG) composed by 80 office workers. Evaluation of subjects included a questionnaire on chronic respiratory symptoms, lung function tests, COPD diagnostics, and measurement of CRP serum concentrations.RESULTS:Serum CRP concentrations were raised in stable COPD patients independent of smoking habit or exposure duration. The mean CRP serum concentrations were higher in the subjects of EG1 and EG2 compared with those in CG, but without statistical significance. This count for mean CRP serum concentrations in subjects of EG1 and EG2 exposed more than 20 years and for those in smokers in all three groups as well. The mean CRP serum concentrations were significantly higher in subjects with COPD within EG1 (P=0.049) and EG2 (P=0.040), while those in CG were not.CONCLUSION:Data obtained suggest that systemic inflammation is present in farmers with COPD and CRP is an important biomarker in COPD in means of reflecting disease severity and prognosis of exposed farmers.

Respiratory problems in children with esophageal atresia and tracheoesophageal fistula

BackgroundChildren with congenital esophageal atresia (EA) and tracheoesophageal fistula (TEF) have chronic respiratory symptoms including recurrent pneumonia, wheezing and persistent cough. The aim of this study is to describe the clinical findings of a large group of children with EA and TEF surgically corrected and the instrumental investigation to which they have undergone in order to better understand the patient’s needs and harmonize the care.MethodsA retrospective data collection was performed on 105 children with EA and TEF followed at Department of Pediatric Medicine of Bambino Gesù Children’s Hospital (Rome, Italy) between 2010 and 2015.Results69/105 (66%) children reported lower respiratory symptoms with a mean age onset of 2.2 ± 2.5 years and only 63/69 (91%) performed specialist assessment at Respiratory Unit. Recurrent pneumonia (33%) and wheezing (31%) were the most reported symptoms. The first respiratory evaluation was performed after surgically correction of gastroesophageal reflux (GER) at mean age of 3.9 ± 4.2 years. Twenty nine patients have undergone to chest CT with contrast enhancement detecting localized atelectasis (41%), residual tracheal diverticulum (34%), bronchiectasis (31%), tracheal vascular compression (21%), tracheomalacia (17%) and esophageal diverticulum (14%). Fifty three patients have undergone to airways endoscopy detecting tracheomalacia (66%), residual tracheal diverticulum (26%), recurrent tracheoesophageal fistula (19%) and vocal cord paralysis (11%).ConclusionsOur study confirms that respiratory symptoms often complicate EA and TEF; their persistence despite medical and surgical treatment of GER means that other etiological hypothesis must be examined and that a complete respiratory diagnostic work up must be considered.

Human Immunodeficiency Virus-Associated Chronic Lung Disease in Children and Adolescents in Zimbabwe: Chest Radiographic and High-Resolution Computed Tomographic Findings.

Chronic respiratory symptoms are common among children living with human immunodeficiency virus (HIV). We investigated the radiological features of chronic lung disease in children aged 6-16 years receiving antiretroviral therapy for ≥6 months in Harare, Zimbabwe. Consecutive participants from a HIV clinic underwent clinical assessment and chest radiography. Participants with an abnormal chest radiograph (assessed by a clinician) and/or those meeting a clinical case definition for chronic lung disease underwent high-resolution computed tomography (HRCT). Radiological studies were scored independently and blindly by 2 thoracic radiologists. Relationships between radiological abnormalities and lung function were examined. Among 193 participants (46% female; median age, 11.2 years; interquartile range, 9.0-12.8 years), the median CD4 cell count was 720/µL (473-947/µL), and 79% had a human immunodeficiency virus (HIV) load of <400 copies/mL. The most common chest radiographic finding was ring/tramline opacities (55 of 193 participants; 29%). HRCT scans were evaluated in 84 participants (69%); decreased attenuation (present in 43%) was the dominant abnormality seen. The extent of decreased attenuation was strongly correlated with both the severity and extent of bronchiectasis (rs = 0.68 and P < .001 for both). The extent of decreased attenuation was also negatively correlated with forced expiratory volume in first second of expiration (rs = -0.52), forced vital capacity (rs = -0.42), and forced expiratory flow, midexpiratory phase (rs = -0.42) (P < .001 for all). The HRCT findings strongly suggest that obliterative bronchiolitis may be the major cause of chronic lung disease in our cohort. Further studies to understand the pathogenesis and natural history are urgently needed.

Dust exposure and health of workers in duck hatcheries.

The objectives of this cross-sectional study were to investigate dust exposure and respiratory health of workers in duck hatcheries in western France. Ninety volunteer workers, who work in sorting rooms and/or incubation rooms, participated in exposure assessments and medical examinations. Medical examinations were performed by occupational health practitioners.They filled-in a questionnaire with the workers, followed by a lung function test on each worker. General characteristics and prevalence of chronic respiratory symptoms were described in each type of working rooms. Associations between symptoms and exposure (working room or dust level) were studied in GEE multivariate models. Overall prevalence of chronic respiratory symptoms (cough, phlegm) and chronic bronchitis were similar or lower than in the reference population. However, prevalence of these symptoms was higher for those working in sorting rooms, that were associated with an increased risk of respiratory symptoms and decreased lung function. Respirable dust was also significantly associated with an increased risk of respiratory symptoms. The prevalence of asthma and rhinitis were well above those in the reference population, but did not vary among working rooms. Descriptive data suggested an occupational origin for some cases. Hatchery workers were at increased risk of compromised respiratory health due to dust exposure, particularly those who work in sorting rooms. Asthma and rhinitis were in excess in this population of workers. Thorough clinical examination of these workers should be performed and all exposures assessed.

Arterial stiffness in symptomatic smokers with normal lung function.

Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular morbidity and mortality. Arterial stiffness and endothelial dysfunction index are validated surrogate cardiovascular markers and are increased in subjects with COPD.We tested whether increased arterial stiffness and endothelial dysfunction occur in symptomatic smokers with no evidence of bronchial obstruction. Clinical and lung functional assessments were conducted in smoker subjects with chronic respiratory symptoms and in COPD patients. Pulse wave velocity (PWV), aortic augmentation index (AIx) and reactive hyperaemia index (RHI) were measured to estimate the cardiovascular risk.48 smokers (male n=37, female n=11; mean age 70±8.4 years) were studied. Smokers with respiratory symptoms without bronchial obstruction (n=13) did not differ from COPD patients (n=35) in terms of mean±sd PWV (12±3.2 m·s−1 versus 14±3.8 m·s−1; p=0.10), aortic AIx (25.2±11.8% versus 24.8±9.7%, p=0.89) and RHI (1.66±1.49 versus 1.62±1.43; p=0.79).The current investigation shows that the cardiovascular risk occurs in smokers with respiratory symptoms in the absence of bronchial obstruction. These findings need to be confirmed in larger populations in order to inform the design of intensive preventive programmes.

SSRI/SNRI ANTI-DEPRESSANT INDUCED INTERSTITIAL LUNG DISEASE: A CASE SERIES AND CASE- CONTROL STUDY

SSRI and SNRI anti-depressants are widely prescribed in the elderly population. For unknown reasons, the incidence of interstitial lung disease (ILD) is increasing in western populations. There are published case reports and references on the Pneumotox web site (www.pneumotox.com) linking SSRIs/SNRIs to development of ILD and/or airway involvement (ILD/AWI). A case of venlafaxine induced ILD/AWI led us to explored this association in more detail. We report a series of 5 cases and a case control study examining the association between SSRI/SNRI usage and presence of ILD/AWI in an elderly population. Participants were all 296 elderly people followed in a primary care geriatric practice. A chart audit of the electronic medical record was done to identify cases and controls. The case definition included chronic respiratory symptoms and presence of ILD/AWI on CT or CXR. SSRI/SNRI usage was standardized to 10mg of citalopram and person-month (p-m) exposure was calculated. There were 24 cases identified and 272 controls. Their mean ages were 90.5 and 88.6 (ns) respectively. There were 16/24 cases exposed to SSRI/SNRI and 97/175 controls. The Odds Ratio was 3.61, 95% CI 1.49–8.74, p 0.007. The mean p-m exposure to SSRI/SNRI was 129.3 months for cases and 27.1 for controls (P<0.001). We conclude that SSRIs and SNRIs were significantly associated with the risk of ILD/AWI. Because of their wide spread usage, further studies should be done to validate these findings. Prescribers should be cautious to monitor for development of insidious pulmonary symptoms and signs when these drugs are prescribed.

Predicting risk of undiagnosed COPD: development and validation of the TargetCOPD score.

Chronic obstructive pulmonary disease (COPD) is greatly underdiagnosed worldwide and more efficient methods of case-finding are required. We developed and externally validated a risk score to identify undiagnosed COPD using primary care records.We conducted a retrospective cohort analysis of a pragmatic cluster randomised controlled case-finding trial in the West Midlands, UK. Participants aged 40-79 years with no prior diagnosis of COPD received a postal or opportunistic screening questionnaire. Those reporting chronic respiratory symptoms were assessed with spirometry. COPD was defined as presence of relevant symptoms with a post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal. A risk score was developed using logistic regression with variables available from electronic health records for 2398 participants who returned a postal questionnaire. This was externally validated among 1097 participants who returned an opportunistic questionnaire to derive the c-statistic, and the sensitivity and specificity of cut-points.A risk score containing age, smoking status, dyspnoea, prescriptions of salbutamol and prescriptions of antibiotics discriminated between patients with and without undiagnosed COPD (c-statistic 0.74, 95% CI 0.68-0.80). A cut-point of ≥7.5% predicted risk had a sensitivity of 68.8% (95% CI 57.3-78.9%) and a specificity of 68.8% (95% CI 65.8.1-71.6%).A novel risk score using routine data from primary care electronic health records can identify patients at high risk for undiagnosed symptomatic COPD. This score could be integrated with clinical information systems to help primary care clinicians target patients for case-finding.

More Evidence Linking Smoke-Free Legislation and Lower Risk of Prematurity and Low Birth Weight.

Premature and low birth weight infants have increased mortality and morbidities including chronic respiratory symptoms, neurocognitive deficits, feeding difficulties, and retinopathy of prematurity. These sequelae often result in prolonged hospitalizations, frequent readmissions, and need for subspecialty care. Direct and indirect costs for the care of these children can be significant. Reduction of maternal secondhand smoke exposure during pregnancy has been identified as a modifiable risk factor for both preterm and low birth weight infants. The most recent US Surgeon General’s report on secondhand smoke noted a causal relationship between maternal exposure to secondhand smoke and a reduction in birth weight as well as a suggestive relationship between the same exposure and preterm delivery,1 underscoring the … Address correspondence to Karen M. Wilson, MD, MPH, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1198, New York, NY 10029. E-mail: karen.wilson{at}mssm.edu

The diagnosis of cystic fibrosis

Establishing the diagnosis of cystic fibrosis (CF) is straight forward in the majority of patients: they present with a clear clinical picture (most frequently chronic respiratory symptoms plus malabsorption), the sweat chloride value is>60mmol/L and two known disease causing CFTR mutations are identified. In less than 5% of subjects, mainly those with a milder or limited phenotype, the diagnostic process is more complex, because initial diagnostic test results are inconclusive: sweat chloride concentration in the intermediate range, less than 2 CF causing mutations identified or both. These patients should be referred to expert centers where bioassays of CFTR function like nasal potential difference measurement or intestinal current measurement can be done. Still, in some patients, despite symptoms compatible with CF and some indication of CFTR dysfunction (e.g. only intermediate sweat chloride value), diagnostic criteria are not met (e.g. only 1 CFTR mutation identified). For these subjects, the term CFTR related disorder (CFTR-RD) is used. Patients with disseminated bronchiectasis, congenital bilateral absence of the vas deferens and acute or recurrent pancreatitis may fall in this category. CF has a very wide disease spectrum and increasingly the diagnosis is being made during adult life, mainly in subjects with milder phenotypes. In many countries, nationwide CF newborn screening (NBS) has been introduced. In screen positive babies, the diagnosis of CF must be confirmed by a sweat test demonstrating a sweat chloride concentration above 60mmol/L. To achieve the benefit of NBS, every baby in whom the diagnosis of CF is confirmed must receive immediate follow-up and treatment in a CF reference center. CF NBS is not full proof: some diagnoses will be missed and in some babies the diagnosis cannot be confirmed nor ruled out with certainty. Screening algorithms that include gene sequencing will detect a high number of such babies that are screen positive with an inconclusive diagnosis (CFSPID). Even in 2016, the most reliable and widely available diagnostic test for CF is the measurement of chloride concentration in sweat. The method of choice is sweat induction by pilocarpine iontophoresis, followed by sweat collection on a gauze or filter paper or in a Macroduct coil. Since mutation specific therapies have become available, it is important to identify the mutations responsible for CF in each individual patient.

Air pollution and respiratory health among diabetic and non-diabetic subjects in Pune, India-results from the Wellcome Trust Genetic Study.

Diabetics may be more vulnerable to the harmful effects of ambient air pollutants than healthy individuals. But, the risk factors that lead to susceptibility to air pollution in diabetics have not yet been identified. We examined the effect of exposure to ambient PM10 on chronic symptoms and the pulmonary function tests (PFT) in diabetic and non-diabetic subjects. Also, to investigate possible determinants of susceptibility, we recruited 400 type 2 diabetic and 465 healthy subjects who were investigated for chronic respiratory symptoms (CRSs) and then underwent measurement of forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) according to standard protocol. Percent predicted FEV1 and FVC (FEV1% and FVC%, respectively) for each subject were calculated. Particulate matter (PM10) concentrations at residence place of subjects were estimated using AERMOD dispersion model. The association between PM10 and CRSs was explored using logistic regression. We also used linear regression models controlling for potential confounders to study the association between chronic exposure to PM10 and FEV1% and FVC%. Prevalence of current wheezing, allergy symptom, chest tightness, FEV1/FVC <70%, and physician-diagnosed asthma and COPD was significantly higher among diabetic subjects than non-diabetics. There was no significant difference between percent predicted value of PFT among diabetic and non-diabetic subjects (P<0.05). We estimated that 1 SD increase in PM10 concentration was associated with a greater risk of having dyspnea by 1.50-fold (95% CI, 1.12-2.01). Higher exposure to PM10 concentration was also significantly associated with lower FVC%. The size of effect for 1 SD μg/m3 (=98.38) increase in PM10 concentration was 3.71% (95% CI, 0.48-4.99) decrease in FVC%. In addition, we indicated that strength of these associations was higher in overweight, smoker, and aged persons. We demonstrated a possible contribution of air pollution to reduced lung function independent of diabetes status. This study suggests that decline in exposure may significantly reduce disease manifestation as dyspnea and impaired lung function. We conduct that higher BMI, smoking, and older age were associated with higher levels of air pollution effects.

Clinical and Genetic Associations of Objectively Identified Interstitial Changes in Smokers

Smoking-related lung injury may manifest on CT scans as both emphysema and interstitial changes. We have developed an automated method to quantify interstitial changes and hypothesized that this measurement would be associated with lung function, quality of life, mortality, and a mucin 5B (MUC5B) polymorphism. Using CT scans from the Genetic Epidemiology of COPD Study, we objectively labeled lung parenchyma as a tissue subtype. We calculated the percentage of the lung occupied by interstitial subtypes. A total of 8,345 participants had clinical and CT scanning data available. A 5%absolute increase in interstitial changes was associated with an absolute decrease in FVC%predicted of 2.47%(P< .001) and a 1.36-point higher St. George's Respiratory Questionnaire score (P< .001). Among the 6,827 participants with mortality data, a 5%increase in interstitial changes was associated with a 29%increased risk of death (P<.001). These associations were present in a subgroup without visually defined interstitial lung abnormalities, as well as in those with normal spirometric test results, and in those without chronic respiratory symptoms. In non-Hispanic whites, for each copy of the minor allele of the MUC5B promoter polymorphism, there was a 0.64% (P < .001) absolute increase in the percentage of lung with interstitial changes. Objective interstitial changes on CT scans were associated with impaired lung function, worse quality of life, increased mortality, and more copies of a MUC5B promoter polymorphism, suggesting that these changes may be a marker of susceptibility to smoking-related lung injury, detectable even in those who are healthy by other measures.

Interstitial lung disease of infancy caused by a new NKX2‐1 mutation

Key Clinical MessagePatients with personal or family history of congenital hypothyroidism, and/or neurological findings that also have chronic respiratory symptoms may have a mutation in the NKX2.1 gene as the unifying cause of their disease. Brain–lung–thyroid disease is the ensuing condition, which although rare, needs to be part of the differential diagnosis.