scholarly journals Longitudinal assessment of loss and gain of lung function in childhood asthma

2021 ◽  
Author(s):  
Bruno Mahut ◽  
Plamen Bokov ◽  
Nicole Beydon ◽  
Christophe Delclaux
Keyword(s):  
Lung Function ◽  
Childhood Asthma ◽  
Management Program ◽  
Rate Of Change ◽  
Negative Slope ◽  
P Value ◽  
Longitudinal Assessment ◽  
Loss Of Function ◽  
Positive Slope

Background: The Childhood Asthma Management Program study revealed that 25.7% of children with mild to moderate asthma exhibit a loss of lung function. The objective was to assess the trajectories of function by means of serial FEV1 in asthmatic children participating in out-of-hospital follow-up. Methods: A total of 295 children (199 boys) who had undergone at least 10 spirometry tests from the age of 8 were selected from a single-center open cohort. The annualized rate of change (slope) for prebronchodilator FEV1 (percent predicted) was estimated for each participant and three patterns were defined: significantly positive slope, significantly negative slope, and null slope (non-significant P-value in the Pearson test). The standard deviation (SD) of each individual slope was recorded as a variability criterion of FEV1. Results: The median (25th and 75th percentile) age at inclusion and the last visit was 8.5 (8.2, 9.3) and 15.4 (14.8, 16.0) years, respectively. Tracking of function (null slope) was observed in 68.8% of the children, while 27.8% showed a loss of function (negative slope) and 3.4% showed a gain in function (positive slope). The children characterized by loss of function depicted a better initial function and a lower FEV1 variability during their follow-up than children with tracking or gain of lung function. At the last visit, these children were characterized by a lower lung function than children with tracking or gain of lung function. Conclusion: Children with a better initial FEV1 value and less FEV1 variability are more prone to loss of lung function.

scholarly journals A de novo paradigm for male infertility

2021 ◽  
Author(s):  
MS Oud ◽  
RM Smits ◽  
HE Smith ◽  
FK Mastrorosa ◽  
GS Holt ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
P Value ◽  
Missense Mutations ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Systematic Analysis ◽  
Significant Enrichment

IntroductionDe novo mutations (DNMs) are known to play a prominent role in sporadic disorders with reduced fitness1. We hypothesize that DNMs play an important role in male infertility and explain a significant fraction of the genetic causes of this understudied disorder. To test this hypothesis, we performed trio-based exome-sequencing in a unique cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare protein altering DNMs were classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of Loss-of-Function (LoF) DNMs in LoF-intolerant genes (p-value=1.00×10-5) as well as predicted pathogenic missense DNMs in missense-intolerant genes (p-value=5.01×10-4). One DNM gene identified, RBM5, is an essential regulator of male germ cell pre-mRNA splicing2. In a follow-up study, 5 rare pathogenic missense mutations affecting this gene were observed in a cohort of 2,279 infertile patients, with no such mutations found in a cohort of 5,784 fertile men (p-value=0.009). Our results provide the first evidence for the role of DNMs in severe male infertility and point to many new candidate genes affecting fertility.

scholarly journals Reduced Lung Function and Progression to Prediabetes: A Prospective Study

2021 ◽  
Author(s):  
Ovais Karnain Wadoo ◽  
Ishtiaq Ahmad ◽  
Sheikh Imran Sayeed
Keyword(s):  
Lung Function ◽  
Glucose Tolerance ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
Forced Expiratory Volume ◽  
P Value ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Lung Dysfunction

Objective: Prediabetes is a state that people have blood glucose levels higher than normal but still not in diabetes range. There is a close relationship between impaired lung function and diabetes mellitus (DM). Reduced lung function can be present before the clinical evidence of diabetes or insulin resistance. Materials and Methods: The total number of subjects in this longitudinal study was 503 and compared with apparently healthy Kashmiri adults. All the subjects, at the time of their first visit, underwent Fasting Plasma Glucose (FPG) estimation, 2- hour oral glucose tolerance test (OGTT) and spirometry (FVC, FEV1 & FEV1/FVC). Those subjects who had normal glucose tolerance (NGT) were retested for glycemic status and spirometric values after a follow-up period of 2-18 (mean=10) months. Results: Out of total 503 subjects on follow up 483 (96%) had NGT and 20 (4%) had prediabetes. Percent predicted forced vital capacity (FVC) and % predicted forced expiratory volume in 1st second (FEV1) were significantly lower (P-value< 0.001) while as % predicted FEV1/FVC was significantly higher (P-value< 0.001) in prediabetes as compared to NGT group. Conclusion: Results of our study point out a predominantly restrictive pattern of lung dysfunction in the prediabetes group as compared to the NGT group.

Accelerated decline in lung function in adults with a history of remitted childhood asthma

2021 ◽  
pp. 2100305
Author(s):  
Shinichiro Miura ◽  
Hiroshi Iwamoto ◽  
Keitaro Omori ◽  
Kakuhiro Yamaguchi ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Lung Function ◽  
Childhood Asthma ◽  
Later Life ◽  
Forced Expiratory Volume ◽  
Normal Lung ◽  
Rapid Decline ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
History Of

AimA significant number of children with asthma show remission in adulthood. Although these adults are often diagnosed with chronic obstructive pulmonary disease in later life, the effect of clinically remitted childhood asthma on the decline in lung function during adulthood is uncertain. We examined whether clinical remission of childhood asthma was associated with an accelerated decline in lung function in apparently non-asthmatic adults.MethodsHere, 3584 participants (mean age, 48.1 years; range, 35–65 years) who did not have adulthood asthma and other lung diseases and had normal lung function at the baseline visit were included. They were categorised as follows: those with remitted childhood asthma (n=121) and healthy controls (n=3463) according to their self-reported childhood asthma history. Spirometry was performed at baseline and follow-up visits.ResultsThe mean follow-up time was 5.3 years. Multivariate regression analysis showed that remitted childhood asthma and smoking were independently associated with a rapid decline in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Besides, smoking was an independent predictor of a rapid decline in the FEV1/FVC. The annual decline in FEV1 and FVC was significantly greater in participants with remitted childhood asthma than in healthy controls, and the differences remained significant after adjusting for the propensity score.ConclusionA history of clinically remitted childhood asthma is an independent risk factor for accelerated decline in lung function in adults. Remitted childhood asthma and smoking may additively accelerate the development of obstructive lung disease.

scholarly journals An exploratory study of the associations between maternal iron status in pregnancy and childhood wheeze and atopy

2014 ◽  
Vol 112 (12) ◽  
pp. 2018-2027 ◽  
Author(s):  
Bright I. Nwaru ◽  
Helen Hayes ◽  
Lorraine Gambling ◽  
Leone C. A. Craig ◽  
Keith Allan ◽  
...  
Keyword(s):  
Lung Function ◽  
Childhood Asthma ◽  
Iron Status ◽  
Atopic Disease ◽  
First Trimester ◽  
Forced Expiratory Volume ◽  
Maternal Serum ◽  
Fetal Ultrasound ◽  
Increased Risk

Maternal nutritional status during pregnancy has been reported to be associated with childhood asthma and atopic disease. The Avon Longitudinal Study of Parents and Children has reported associations between reduced umbilical cord Fe status and childhood wheeze and eczema; however, follow-up was short and lung function was not measured. In the present study, the associations between maternal Fe status during pregnancy and childhood outcomes in the first 10 years of life were investigated in a subgroup of 157 mother–child pairs from a birth cohort with complete maternal, fetal ultrasound, blood and child follow-up data. Maternal Fe intake was assessed using FFQ at 32 weeks of gestation and Hb concentrations and serum Fe status (ferritin, soluble transferrin receptor and TfR-F (transferrin receptor:ferritin) index) were measured at 11 weeks of gestation and at delivery. Maternal Fe intake, Hb concentrations and serum Fe status were found to be not associated with fetal or birth measurements. Unit increases in first-trimester maternal serum TfR concentrations (OR 1·44, 95 % CI 1·05, 1·99) and TfR-F index (OR 1·42, 95 % CI 1·10, 1·82) (i.e. decreasing Fe status) were found to be associated with an increased risk of wheeze, while unit increases in serum ferritin concentrations (i.e. increasing Fe status) were found to be associated with increases in standardised mean peak expiratory flow (PEF) (β 0·25, 95 % CI 0·09, 0·42) and forced expiratory volume in the first second (FEV1) (β 0·20, 95 % CI 0·08, 0·32) up to 10 years of age. Increasing maternal serum TfR-F index at delivery was found to be associated with an increased risk of atopic sensitisation (OR 1·35, 95 % CI 1·02, 1·79). The results of the present study suggest that reduced maternal Fe status during pregnancy is adversely associated with childhood wheeze, lung function and atopic sensitisation, justifying further studies on maternal Fe status and childhood asthma and atopic disease.

Reversive Loss of Pulmonary Function Induced by Acute Chest Syndrome: A Report from the National Acute Chest Syndrome Study Group (NACSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 315-315 ◽  
Author(s):  
Lynne Neumayr ◽  
C. Morris ◽  
A. Wen ◽  
A. Earles ◽  
S. Robertson ◽  
...  
Keyword(s):  
Lung Function ◽  
Pulmonary Function ◽  
Pulmonary Function Tests ◽  
Forced Expiratory Volume ◽  
Therapeutic Interventions ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Lung Volumes ◽  
Expiratory Flow

Abstract Acute Chest Syndrome (ACS) remains the leading cause of death and hospitalization in patients (pts) with sickle cell disease (SCD). There is limited data on the effects of ACS on lung function. From 1993 to 1997, 30 centers participated in the NACSG and prospectively analyzed 671 episodes of ACS in 538 pts. Pulmonary function tests (PFTs) included forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), forced expiratory flow during 25% to 75% of FVC (FEF 25–75), peak expiratory flow rate (PEF) and the ratio of FEV1/FVC. Data is reported as percent-predicted of normal values based on age and height. 128 pts (mean 16yrs, 4 to 52 yr range) had PFTs during an ACS episode (within a mean of 2.5 days of diagnosis) and then 12 weeks later. 94% of pts had abnormal lung volumes, defined as either FEV1 or FVC < 80%. Mean lung volumes during ACS and at follow-up are shown below. Table 1: Decreased Lung Volumes During ACS PFT During ACS Follow-up p-value FEV1 52% 79% <.0001 FVC 55% 83% <.0001 FEF 25–75 50% 69% <.0001 PEF 61% 83% <.0001 Pts with abnormal lung volumes (FEV1 or FVC < 80%) and considered to have an obstructive pattern if the FEV1/FVC ratio was < to 85. Obstructive patterns in pts with abnormal lung volumes and the percent of pts who responded to bronchodilators (15% improvement in either FEV1 or FVC) are shown below. Table 2: Patterns of Abnormal Lung Volumes in SCD SCD Patients During ACS Follow-up Abnormal PFTs 94% 45% Obstructive Pattern 48% 46% Respond to bronchodilators 25% 8% In summary, ACS resulted in decreased pulmonary function in 94% of pts. It is striking that 49% pts had their PFTs reduced by half (FEV1 52% and FVC 55%). In pts with abnormal PFTs, 48% had evidence of obstruction and 25% of all pts tested improved with a bronchodilator. This is the first description of reversible abnormalities of pulmonary function occurring during ACS compared to baseline. An obstructive pattern is identified in a higher percentage of pts with SCD than in the local Oakland African American population (asthma prevalance 16%). While some pts PFTs improved with time, 45% remained abnormal at 12-week follow-up. ACS results in acute and chronic worsening of lung function. Future studies of ACS may reveal common pathogenic mechanisms with asthma, and lead to improved therapeutic interventions.

scholarly journals A Novel Locus for Exertional Dyspnea in Childhood Asthma

2020 ◽  
pp. 2001224
Author(s):  
Sanghun Lee ◽  
Jessica Ann Lasky-Su ◽  
Christoph Lange ◽  
Wonji Kim ◽  
Preeti Lakshman Kumar ◽  
...  
Keyword(s):  
Childhood Asthma ◽  
Respiratory Symptoms ◽  
Association Studies ◽  
Management Program ◽  
Costa Rican ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Exertional Dyspnea ◽  
Genome Wide ◽  
A Genome

BackgroundMost children diagnosed with asthma suffer from respiratory symptoms such as cough, dyspnea, and wheezing which are also important markers of overall respiratory function. A decade of genome-wide association studies (GWAS) have investigated the genetic susceptibility of asthma diagnosis itself, but few have focused on important respiratory symptoms that characterise childhood asthma.MethodUsing whole-genome sequencing (WGS) data for 894 asthmatic trios from a Costa Rican cohort, we performed family-based association tests (FBATs) to assess the association between genetic variants and multiple asthma-relevant respiratory phenotypes: cough, phlegm, wheezing, exertional dyspnea, and exertional chest tightness. We tested whether genome-wide significant associations replicated in two additional studies: 1) 286 WGS trios from the Childhood Asthma Management Program (CAMP), and 2) 2691 African American (AA) current or former smokers from the COPDGene study.ResultsIn the 894 Costa Rican trios, we identified a genome-wide significant association between exertional dyspnea and single nucleotide polymorphism (SNP) rs10165869, located on chromosome 2q37.3 with a p value of 3.49×10−9 that was replicated in the CAMP cohort (p=0.0222) with the same direction of association (combined p=5.54×10−10), but was not associated in the AA subjects from COPDGene. We also found suggestive evidence of a link between SNP rs10165869 and the atypical chemokine receptor 3 (ACKR3) for the biological interpretation.ConclusionWe identified and replicated a novel association between exertional dyspnea and SNP rs10165869 in childhood asthma which encourages to discover respiratory symptom associated variants in various airway diseases.

scholarly journals Longitudinal assessment of loss and gain of lung function in childhood asthma

2021 ◽  
pp. 1-10
Author(s):  
Bruno Mahut ◽  
Plamen Bokov ◽  
Nicole Beydon ◽  
Christophe Delclaux
Keyword(s):  
Lung Function ◽  
Childhood Asthma ◽  
Longitudinal Assessment

scholarly journals A de novo paradigm for male infertility

2021 ◽  
Author(s):  
Joris Veltman ◽  
Manon Oud ◽  
Roos Smits ◽  
Hannah Smith ◽  
Francesco Mastrorosa ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
P Value ◽  
Missense Mutations ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Systematic Analysis ◽  
Significant Enrichment

Abstract De novo mutations (DNMs) are known to play a prominent role in many sporadic disorders with reduced fitness. We hypothesize that DNMs play an important role in male infertility and explain a significant fraction of the genetic causes of this understudied disorder. We performed a trio-based exome-sequencing study in a unique cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare protein altering DNMs were classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of Loss-of-Function (LoF) DNMs in LoF-intolerant genes (p-value=1.00x10-5) as well as predicted pathogenic missense DNMs in missense-intolerant genes (p-value=5.01x10-4). One DNM gene identified, RBM5, is an essential regulator of male germ cell pre-mRNA splicing. In a follow-up study, 5 rare pathogenic missense mutations affecting this gene were observed in a cohort of 2,279 infertile patients, with no such mutations found in a cohort of 5,784 fertile men (p-value=0.009). Our results provide the first evidence for the role of DNMs in severe male infertility and point to many new candidate genes affecting fertility.

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