Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45–1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify “high-risk” infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.

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The effect of age and genotype on lung function in children with cystic fibrosis

Russian Pulmonology ◽

10.18093/0869-0189-2021-31-2-159-166 ◽

2021 ◽

Vol 31 (2) ◽

pp. 159-166

Author(s):

V. V. Shadrina ◽

A. Yu. Voronkova ◽

M. A. Starinova ◽

O. I. Simonova ◽

D. F. Sergienko ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Russian Federation ◽

Age Groups ◽

Forced Expiratory Volume ◽

Functional Disorders ◽

Significant Difference ◽

The Russian Federation ◽

Effect Of Age ◽

Adolescent Period

Identifying the initial manifestations of pulmonary functional disorders associated with cystic fibrosis (CF) is essential for timely correction of the therapy and improvement of the prognosis.The aim of the study was to identify the age periods with the highest risk of a decrease in lung function in children with different CF genotypes.Methods. Lung function (LF) was analyzed using spirometry results in CF patients aged 6 to 18 years from the Registry of patients with cystic fibrosis in the Russian Federation 2018.Results. The forced expiratory volume in one second (FEV1) was statistically significantly lower in children aged 6 – 10 years with “severe” genotypes than in the children with “mild” genotypes. The lung function was reduced at 11 – 14 years of age in both “severe» and “mild” genotypes without any statistically significant difference. In general, the trend of a decrease in lung function in “severe” genotypes persists in the adolescent period from 15 to 18 years. The lung function is better in adolescents aged 15 – 18 with the “mild” variants of genotypes compared to the patients aged 11 – 14 years.Conclusion. The “severe” variants of CFTR negatively affect LF of CF patients in all age groups. The LF values in patients with “mild” genotypes at the age of 15 – 18 years were higher than in children aged 11 – 14 years with the same genotypes. There is a need for improved programs of medical care for adolescents with CF.

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Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

Journal of Applied Physiology ◽

10.1152/japplphysiol.00209.2002 ◽

2002 ◽

Vol 93 (4) ◽

pp. 1384-1390 ◽

Cited By ~ 54

Author(s):

Emanuele Crimi ◽

Riccardo Pellegrino ◽

Manlio Milanese ◽

Vito Brusasco

Keyword(s):

Forced Vital Capacity ◽

Healthy Subjects ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Forced Expiration ◽

Airway Narrowing ◽

Significant Difference ◽

Mild Asthmatic ◽

Residual Capacity ◽

Airway Conductance

Deep breaths taken before inhalation of methacholine attenuate the decrease in forced expiratory volume in 1 s and forced vital capacity in healthy but not in asthmatic subjects. We investigated whether this difference also exists by using measurements not preceded by full inflation, i.e., airway conductance, functional residual capacity, as well as flow and residual volume from partial forced expiration. We found that five deep breaths preceding a single dose of methacholine 1) transiently attenuated the decrements in forced expiratory volume in 1 s and forced vital capacity in healthy ( n = 8) but not in mild asthmatic ( n = 10) subjects and 2) increased the areas under the curve of changes in parameters not preceded by a full inflation over 40 min, during which further deep breaths were prohibited, without significant difference between healthy ( n = 6) and mild asthmatic ( n = 16) subjects. In conclusion, a series of deep breaths preceding methacholine inhalation significantly enhances bronchoconstrictor response similarly in mild asthmatic and healthy subjects but facilitates bronchodilatation on further full inflation in the latter.

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Impaired Lung Functions Using Tidal Breath Analysis in High-risk Infants with Recurrent Wheezing

Trends in Pediatrics ◽

10.5222/tp.2020.43153 ◽

2020 ◽

Author(s):

Ayşe Anık ◽

Pınar Uysal

Keyword(s):

High Risk ◽

Lung Function ◽

Breath Analysis ◽

Roc Curve Analysis ◽

Recurrent Wheezing ◽

Mean Values ◽

Significant Difference ◽

Lung Functions ◽

Lower Lung ◽

High Risk Infants

INTRODUCTION: We aimed to investigate lung functions using tidal breath analysis (TBA) in high-risk infants with recurrent wheezing. METHODS: Lung functions measured using TBA in infants with physician-diagnosed recurrent wheezing (≥3 episodes) who applied our institution between 2018-2020, were retrospectively analyzed. Infants were assigned to two groups: high-risk infants with recurrent wheezing (n=30) and wheezy infants without high risk of atopy (n=33). RESULTS: High-risk infants with recurrent wheezing had lower mean values of tPTEF, tPTEF: tE, VPTEF, and VPTEF: VE than that of wheezy infants without high risk of atopy. There was no significant difference between two groups in terms of Vt/kg and respiratory rate. ROC curve analysis showed that tPTEF: tE ratio <26.5 demonstrated 63.3% sensitivity and 63.6% specificity for detection of high risk of atopy. DISCUSSION AND CONCLUSION: This study showed that high-risk infants with recurrent wheezing have lower lung function than those of wheezy infants without high risk of atopy. TBA might be useful method to evaluate lung function in wheezy infants.

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Impact of chronic khat (Catha edulis Forsk) chewing on pulmonary function test and oxygen saturation in humans: A comparative study

SAGE Open Medicine ◽

10.1177/2050312118824616 ◽

2019 ◽

Vol 7 ◽

pp. 205031211882461 ◽

Cited By ~ 1

Author(s):

Gashaw Garedew Woldeamanuel ◽

Teshome Gensa Geta

Keyword(s):

Lung Function ◽

Pulmonary Function ◽

Oxygen Saturation ◽

Vital Capacity ◽

Forced Expiratory Volume ◽

Mean Values ◽

Khat Chewing ◽

Significant Difference ◽

The Mean

Background: Chronic consumption of khat affects many organ systems and leads to various health disturbances in the chewers. Few studies examined the acute effects of khat ingestion on lung function parameters. However, studies which assessed the long-term effects of khat chewing on pulmonary function parameters and oxygen saturation are lacking. Objective: The aim of this study was to assess the impact of chronic Khat chewing on pulmonary function parameters and oxygen saturation among chronic Khat chewers in Wolkite, Ethiopia. Methods: A community-based comparative cross-sectional study was conducted in Wolkite, Ethiopia from 1 June 2018 to 15 August 2018. A total of 324 participants, 162 khat chewers and 162 non-chewers were included in the study. The data were collected through face-to-face interview by trained data collectors. British Medical Research Council respiratory questionnaire was used to assess respiratory symptoms. A spirometer was used to assess various lung function parameters. Moreover, oxygen saturation of hemoglobin was measured using pulse oximeter. Data were entered into CSPro version 6.2 and analyzed using SPSS version 23. Results: This study showed statistically significant (p < 0.05) reduction in the mean values of forced vital capacity, forced expiratory volume in first second and maximum ventilation volume among khat chewers as compared to non-chewers. There was no significant difference in the mean values of other lung function parameters between the two groups. Similarly, there was no significant difference (p = 0.642) in mean oxygen saturation of hemoglobin (SaO2) across the two groups. Conclusion: It is evident from this study that long-term khat consumption is associated with decreased mean forced vital capacity, forced expiratory volume in first second and maximum ventilation volume. Hence, there is a need for further study to strengthen the current findings and to explore the mechanisms of khat chewing effect on lung function parameters.

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Integrating latent classes in the Bayesian shared parameter joint model of longitudinal and survival outcomes

Statistical Methods in Medical Research ◽

10.1177/0962280220924680 ◽

2020 ◽

Vol 29 (11) ◽

pp. 3294-3307

Author(s):

Eleni-Rosalina Andrinopoulou ◽

Kazem Nasserinejad ◽

Rhonda Szczesniak ◽

Dimitris Rizopoulos

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Latent Class ◽

Joint Model ◽

Forced Expiratory Volume ◽

Optimal Number ◽

Latent Classes ◽

Joint Models ◽

Number Of Classes ◽

Strength Of Association

Cystic fibrosis is a chronic lung disease requiring frequent lung-function monitoring to track acute respiratory events (pulmonary exacerbations). The association between lung-function trajectory and time-to-first exacerbation can be characterized using joint longitudinal-survival modeling. Joint models specified through the shared parameter framework quantify the strength of association between such outcomes but do not incorporate latent sub-populations reflective of heterogeneous disease progression. Conversely, latent class joint models explicitly postulate the existence of sub-populations but do not directly quantify the strength of association. Furthermore, choosing the optimal number of classes using established metrics like deviance information criterion is computationally intensive in complex models. To overcome these limitations, we integrate latent classes in the shared parameter joint model through a fully Bayesian approach. To choose the optimal number of classes, we construct a mixture model assuming more latent classes than present in the data, thereby asymptotically “emptying” superfluous latent classes, provided the Dirichlet prior on class proportions is sufficiently uninformative. Model properties are evaluated in simulation studies. Application to data from the US Cystic Fibrosis Registry supports the existence of three sub-populations corresponding to lung-function trajectories with high initial forced expiratory volume in 1 s ( FEV1), rapid FEV1 decline, and low but steady FEV1 progression. The association between FEV1 and hazard of exacerbation was negative in each class, but magnitude varied.

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1014 Relationship Between Lung Function and Obstructive Sleep Apnea in Cystic Fibrosis

SLEEP ◽

10.1093/sleep/zsaa056.1010 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A385-A385

Author(s):

A Shakkottai ◽

S Z Nasr ◽

F Hassan ◽

L M O’Brien ◽

R D Chervin

Keyword(s):

Cystic Fibrosis ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Lung Function ◽

Forced Expiratory Volume ◽

Apnea Hypopnea Index ◽

Lung Function Decline ◽

Obstructive Sleep ◽

Larger Sample ◽

Training Grant

Abstract Introduction The frequency of obstructive sleep apnea (OSA) may be high among patients with cystic fibrosis (CF), a life-shortening, genetic respiratory disease that affects approximately 30,000 Americans. Yet, the potential relationship between OSA and lung function has not been thoroughly explored. Methods Single-center retrospective review of polysomnography (PSG) results from 2009-2017 in referred patients with CF and available pulmonary function data (PFTs) obtained at time of PSG and at 3, 6, 9, and 12-months prior. Results Mean ages were 11.1±3.9 (sd) and 37.1±14.1 years, among 18 children and 16 adults, respectively. Mean body mass index (BMI) was normal in both groups (62.5±26.6% in children; 25.1±6.4 kg/m2 in adults). Twenty-six subjects (76%) had OSA (apnea-hypopnea index >1 in children, ≥5 in adults). Mean forced expiratory volume in 1 second percent predicted (FEV1 PPD) was higher among subjects with vs. without OSA at PSG and at each time-point in the year prior, independent of age and BMI at PSG (longitudinal mixed effects model, β=19.0, SE=8.1, p=0.028). While FEV1 PPD remained unchanged in the non-OSA group, FEV1 PPD at PSG was lower, in comparison to the year prior in subjects with OSA, with the greatest difference observed at 9-months prior to PSG (2-sample t-test, difference of -6.6% vs 0.6% in OSA vs. non-OSA groups respectively, p=0.078). Conclusion The PFTs, as daytime markers of CF lung disease severity, do not seem to reliably predict risk for OSA. In our sample, CF patients with vs. without OSA had better PFTs at baseline but they also showed a greater tendency for decline in PFTs over the year prior to OSA diagnosis. Larger sample size and longer duration of assessment may help, going forward, to assess any potential adverse impact of OSA on lung function decline. Support NIH Training Grant (T32NS007222, F32HL145915)

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Lung function over the life course of paediatric and adult patients with cystic fibrosis from a large multi-centre registry

Scientific Reports ◽

10.1038/s41598-020-74502-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Arul Earnest ◽

Farhad Salimi ◽

Claire E. Wainwright ◽

Scott C. Bell ◽

Rasa Ruseckaite ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Mixed Model ◽

Linear Mixed Model ◽

Pancreatic Insufficiency ◽

Forced Expiratory Volume ◽

Rate Of Change ◽

Data Registry ◽

Mortality Outcome ◽

The Impact

Abstract A key measure of lung function in people with Cystic Fibrosis (CF) is Forced Expiratory Volume in the first second FEV1 percent predicted (FEV1pp). This study aimed to address challenges in identifying predictors of FEV1pp, specifically dealing with non-linearity and the censoring effect of death. Data was obtained from a large multi-centre Australian Cystic Fibrosis Data Registry (ACFDR). A linear mixed model was used to study FEV1pp as the endpoint. There were 3655 patients (52.4% male) included in our study. Restricted cubic splines were used to fit the non-linear relationship between age of visit and FEV1pp. The following predictors were found to be significant in the multivariate model: age of patient at visit, BMI z-score, age interaction with lung transplantation, insulin dependent diabetes, cirrhosis/portal hypertension, pancreatic insufficiency, Pseudomonas aeruginosa infection and baseline variability in FEV1pp. Those with P. aeruginosa infection had a lower mean difference in FEV1pp of 4.7 units, p < 0.001 compared to those who did not have the infection. Joint modelling with mortality outcome did not materially affect our findings. These models will prove useful for to study the impact of CFTR modulator therapies on rate of change of lung function among patients with CF.

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Lung function test in children with left-to-right shunt congenital heart disease

Paediatrica Indonesiana ◽

10.14238/pi58.4.2018.165-9 ◽

2018 ◽

Vol 58 (4) ◽

pp. 165-9

Author(s):

Carolina Kurniawan ◽

Indah Kartika Murni ◽

Sasmito Nugroho ◽

Noormanto Noormanto ◽

Roni Naning

Keyword(s):

Congenital Heart Disease ◽

Pulmonary Hypertension ◽

Heart Disease ◽

Lung Function ◽

Congenital Heart ◽

Vital Capacity ◽

Septal Defect ◽

Forced Expiratory Volume ◽

Significant Difference ◽

Restrictive Lung Function

Background Increased pulmonary blood flow may lead to abnormal lung function in children with left-to-right (L to R) shunt congenital heart disease. This condition has been linked to considerable mortality and morbidity, including reduced lung function. Objective To assess for lung function abnormality in children with L to R shunt congenital heart disease. Methods We conducted a cross-sectional study involving children aged 5-18 years and diagnosed with L to R shunt congenital heart disease at Dr. Sardjito Hospital from March to May 2017. Subjects underwent spirometry tests to measure forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and forced expiratory volume-1 (FEV-1)/forced vital capacity (FVC). Results Of 61 eligible subjects, 30 (49.2%) children had atrial septal defect (ASD), 25 (41%) children had ventricular septal defect (VSD), and 6 (9.8%) children had patent ductus arteriosus (PDA). Spirometry revealed lung function abnormalities in 37 (60.7%) children. Restrictive lung function was documented in 21/37 children, obstructive lung function in 11/37 children, and mixed pattern of lung function abnormality in 5/37 children. Pulmonary hypertension was found in 21 children. There was no significant difference in lung function among children with and without pulmonary hypertension (P=0.072). Conclusion Abnormal lung function is prevalent in 60.7% of children with L to R shunt congenital heart disease, of which restrictive lung function is the most common. There was no significant difference in lung function among children with and without pulmonary hypertension.

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Burkholderia dolosa phenotypic variation during the decline in lung function of a cystic fibrosis patient during 5.5 years of chronic colonization

Journal of Medical Microbiology ◽

10.1099/jmm.0.069849-0 ◽

2014 ◽

Vol 63 (4) ◽

pp. 594-601 ◽

Cited By ~ 9

Author(s):

Ana Sílvia Moreira ◽

Carla P. Coutinho ◽

Pilar Azevedo ◽

Luís Lito ◽

José Melo-Cristino ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Fungal Pathogens ◽

Forced Expiratory Volume ◽

Burkholderia Cenocepacia ◽

Epidemiological Surveillance ◽

Lung Function Decline ◽

Swarming Motility ◽

Systematic Assessment ◽

Chronic Colonization

Although rarely isolated from cystic fibrosis (CF) patients, Burkholderia dolosa is associated with accelerated lung function decline. During 18 years of epidemiological surveillance in the major Portuguese CF centre in Lisbon, only one patient was infected with B. dolosa. Pulmonary deterioration, associated with the evolution of forced expiratory volume in 1 s, occurred during 5.5 years of colonization with this B. dolosa clone (with the new sequence type ST-668). Transient co-colonization with Burkholderia cenocepacia and other bacterial and fungal pathogens occurred, but B. dolosa prevailed until the patient’s death. The systematic assessment of relevant phenotypes for the sequential clonal isolates examined in this retrospective study (14 of B. dolosa and four of B. cenocepacia) showed that they were variants, although in general no isolation time-dependent pattern of alteration was identified. However, the first B. dolosa isolate retrieved was more susceptible to gentamicin, imipenem and tobramycin, and exhibited a higher swarming motility compared with most of the isolates obtained during the later stages of disease progression and antimicrobial therapy.

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Elevated lung clearance index in infants with cystic fibrosis shortly after birth

European Respiratory Journal ◽

10.1183/13993003.00580-2017 ◽

2017 ◽

Vol 50 (5) ◽

pp. 1700580 ◽

Cited By ~ 10

Author(s):

Elisabeth Kieninger ◽

Sophie Yammine ◽

Insa Korten ◽

Pinelopi Anagnostopoulou ◽

Florian Singer ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Specific Treatment ◽

Lung Clearance ◽

Time To Peak ◽

Ventilation Inhomogeneity ◽

Lung Clearance Index ◽

Residual Capacity ◽

Z Scores ◽

Noninvasive Markers

It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening.We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF.We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02–0.60; p=0.034 and 14.5 mL, 95% CI 7.7–21.3 mL; p<0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC.Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.

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