Burkholderia dolosa phenotypic variation during the decline in lung function of a cystic fibrosis patient during 5.5 years of 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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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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Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-015-2474-y ◽

2015 ◽

Vol 34 (11) ◽

pp. 2235-2241 ◽

Cited By ~ 21

Author(s):

M. Noni ◽

A. Katelari ◽

G. Dimopoulos ◽

S.-E. Doudounakis ◽

C. Tzoumaka-Bakoula ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Aspergillus Fumigatus ◽

Lung Function Decline ◽

Chronic Colonization

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Pulmonary exacerbations as a risk factor for lung function decline-experiences of the National Cystic Fibrosis Center

Vojnosanitetski pregled ◽

10.2298/vsp171114005g ◽

2019 ◽

Vol 76 (11) ◽

pp. 1110-1114

Author(s):

Bojana Gojsina ◽

Milan Rodic ◽

Jelena Visekruna ◽

Goran Trajkovic ◽

Aleksandar Sovtic ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Burkholderia Cepacia ◽

Negative Impact ◽

Bacterial Colonization ◽

Forced Expiratory Volume ◽

Lung Function Decline ◽

Pulmonary Exacerbations ◽

Fev1 Decline

Background/Aim. Pulmonary exacerbations have negative impact on clinical course of cystic fibrosis (CF) lung disease being associated with a steeper decline in the lung function, unfavorable prognosis and impaired quality of life. The aim of this study was to determine whether an increased number of exacerbations had influence on the lung function in the patients with CF, as well as to estimate the nutritional status, gender, presence of comorbid conditions and bacterial colonization of airways as predictive factors for pulmonary exacerbations. Methods. This retrospective cohort study included 83 pediatric and adult patients, treated from 2011? 2015 in the Mother and Child Health Institute of Serbia ?Dr Vukan Cupic?. The best result of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in each year of follow-up was taken into account to calculate the five-year trend values of these indicators. The number of exacerbations per year of follow-up and its impact on the FEV1 decline was evaluated. Results. Mean annual decline of FEV1 and FVC were 2.4% and 1.7% respectively. The malnourished patients had the lower initial values of FEV1 and FVC, and more frequent exacerbations in comparison with the normal weight and overweight patients. The frequency of exacerbations was significantly higher in the patients chronically colonized with Burkholderia cepacia (p = 0.023). The increased number of exacerbation was proved to be the most important factor in a prediction of FEV1 decline over time (p = 0.013). Conclusion. Pulmonary exacerbations lead to the more progressive lung function decline in the patients with CF. Malnourishment and chronic airway colonization with Burkholderia cepacia result in more frequent pulmonary exacerbations.

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Oxidative stress in cystic fibrosis patients with Burkholderia cenocepacia airway colonization: relation of 8-isoprostane concentration in exhaled breath condensate to lung function decline

Folia Microbiologica ◽

10.1007/s12223-013-0285-z ◽

2013 ◽

Vol 59 (3) ◽

pp. 217-222 ◽

Cited By ~ 3

Author(s):

Libor Fila ◽

Alžběta Grandcourtová ◽

Jaroslav Chládek ◽

Jaromír Musil

Keyword(s):

Oxidative Stress ◽

Cystic Fibrosis ◽

Lung Function ◽

Exhaled Breath Condensate ◽

Burkholderia Cenocepacia ◽

Exhaled Breath ◽

Lung Function Decline ◽

Breath Condensate ◽

Airway Colonization

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Improving lung function in adolescents with CF by tracking annual rate of lung function decline

BMJ Open Quality ◽

10.1136/bmjoq-2020-001199 ◽

2021 ◽

Vol 10 (3) ◽

pp. e001199

Author(s):

Sydney Schiff ◽

Miah Starks ◽

Rachel W Linnemann

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Forced Expiratory Volume ◽

Rapid Decline ◽

Lung Function Decline ◽

Progressive Decline ◽

Individual Patient Level ◽

Proactive Approach ◽

Level Data ◽

Lung Health

BackgroundFor patients with cystic fibrosis (CF), sustaining lung function through the adolescent years is crucial to slow the progressive decline that leads to significant morbidity and early mortality. This holds true for patients with high per cent predicted forced expiratory volume in 1 s (ppFEV1), as they may receive less vigilant monitoring and treatment. Early identification of lung function decline followed by aggressive treatment can lead to preservation of lung function.InterventionThe Emory+Children’s Pediatric Cystic Fibrosis Program implemented multiple quality improvement (QI) initiatives to identify and aggressively treat adolescent patients with a rapid decline in lung function. These initiatives included (1) lung zones to categorise and highlight lung function decline, (2) individual lung decline tables for quick reference, (3) a lung health algorithm to encourage uniformity, (4) a rapid decliner checklist to identify potential reasons for individual decline and (5) an automated individual patient-level data report and centre scorecard. We tested these interventions with plan–do–study–act cycles and refined as needed.ResultsImplementation of these QI initiatives resulted in overall improvement in lung function and slowing of lung function decline among adolescents with CF . This improvement could be attributed to the more standardised and proactive approach to decreases in lung function and the increased clinician attention to patients with rapid decline, especially for patients with high baseline ppFEV1.

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Lung function and disease severity in cystic fibrosis patients heterozygous for p.Arg117His

ERJ Open Research ◽

10.1183/23120541.00056-2016 ◽

2017 ◽

Vol 3 (1) ◽

pp. 00056-2016 ◽

Cited By ~ 5

Author(s):

Michal Shteinberg ◽

Damian G. Downey ◽

Diane Beattie ◽

John McCaughan ◽

Alastair Reid ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Disease Severity ◽

Pancreatic Insufficiency ◽

Forced Expiratory Volume ◽

Class I ◽

Lung Function Decline ◽

Diagnostic Features ◽

Sweat Chloride ◽

In Trans

Expression of p.Arg117His cystic fibrosis (CF) transmembrane conductance regulator is influenced by a polythymidine (poly-T) tract and a thymidine–guanine (TG) repeat on intron 9, which vary in length and affect exon 10 skipping.We compared clinical characteristics and the rate of progression of lung disease of CF patients carrying the p.Arg117His mutation with different intron 9 varying sequences (poly-T) and mutation classes in trans.Data were collected from patients in Northern Ireland, UK, including diagnostic features, sweat chloride, nutritional status, sputum microbiology, CF-related complications and lung function. Poly-T and TG repeats were determined by PCR. Forced expiratory volume in 1 s (FEV1) decline was determined from linear regression of FEV1 measurements of patients over time.We identified 62 patients with p.Arg117His, 55 with a class I/II mutation in trans and six with p.Arg117His/p.Gly551Asp. 42 patients had 5T and 13 had 7T. All patients had 12 TG repeats. Patients with p.Arg117His-5T had greater lung function decline, sweat chloride concentrations, pancreatic insufficiency and prevalence of Pseudomonas aeruginosa infection compared with patients with p.Arg117His-7T.Lung function decline and disease severity in p.Arg117His is determined by the poly-T tract length and identity of the mutation in trans. Patients with p.Arg117His-5T and a second class I/II mutation have a severity similar to p.Phe508del homozygous patients, although lung function decline is delayed to an older age. There may be linkage disequilibrium between p.Arg117His and 12 TG repeats.

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Lung function decline is associated with serum uric acid in Korean health screening individuals

Scientific Reports ◽

10.1038/s41598-021-89678-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyung-Min Ahn ◽

Suh-Young Lee ◽

So-Hee Lee ◽

Sun-Sin Kim ◽

Heung-Woo Park

Keyword(s):

Uric Acid ◽

Lung Function ◽

Serum Uric Acid ◽

Uric Acid Level ◽

Acid Level ◽

Serum Uric Acid Level ◽

Forced Expiratory Volume ◽

Linear Regression Models ◽

Lung Function Decline ◽

Health Screenings

AbstractWe performed a retrospective cohort study of 19,237 individuals who underwent at least three health screenings with follow-up periods of over 5 years to find a routinely checked serum marker that predicts lung function decline. Using linear regression models to analyze associations between the rate of decline in the forced expiratory volume in 1 s (FEV1) and the level of 10 serum markers (calcium, phosphorus, uric acid, total cholesterol, total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, creatinine, and C-reactive protein) measured at two different times (at the first and third health screenings), we found that an increased uric acid level was significantly associated with an accelerated FEV1 decline (P = 0.0014 and P = 0.037, respectively) and reduced FEV1 predicted % (P = 0.0074 and P = 8.64 × 10–7, respectively) at both visits only in non-smoking individuals. In addition, we confirmed that accelerated forced vital capacity (FVC) and FEV1/FVC ratio declines were observed in non-smoking individuals with increased serum uric acid levels using linear mixed models. The serum uric acid level thus potentially predicts an acceleration in lung function decline in a non-smoking general population.

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