THE SITE OF AIRWAY OBSTRUCTION IN CYSTIC FIBROSIS

Evidence has been presented that some patients with cystic fibrosis have significant amounts of obstruction to the ventilation of portions of lung, as indicated by tests of the distribution of ventilation, but they have little or no evidence of obstruction by conventional measurements of airway resistance.1-5 This discrepancy may be attributed to the fact that various tests of pulmonary function differ in sensitivity with respect to small and large airway obstruction. It is the purpose of the present Commentary to summarize the evidence for this hypothesis and to suggest that differences in the extent to which measurements of airway resistance and distribution of ventilation are altered in patients with cystic fibrosis may be used to localize the site of obstruction and to follow the different stages in the natural history of the pulmonary disease.

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Natural history of glucose tolerance, beta-cell function and peripheral insulin sensitivity in cystic fibrosis patients with fasting euglycemia

Acta Endocrinologica ◽

10.1530/eje.0.1490053 ◽

2003 ◽

Vol 149 (1) ◽

pp. 53-59 ◽

Cited By ~ 58

Author(s):

F Lombardo ◽

F De Luca ◽

M Rosano ◽

C Sferlazzas ◽

C Lucanto ◽

...

Keyword(s):

Cystic Fibrosis ◽

Insulin Sensitivity ◽

Natural History ◽

Glucose Tolerance ◽

Pancreatic Beta Cells ◽

Cell Function ◽

Glucose Levels ◽

Peripheral Insulin Resistance ◽

History Of ◽

Over Time

OBJECTIVE: The loss of pancreatic beta-cells is thought to be one of the principal causes of diabetes mellitus (DM) in cystic fibrosis (CF), but the role of peripheral insulin resistance (IR) in the pathogenesis of DM in CF remains unclear. The aim of this study was to evaluate whether eventual changes of glucose tolerance (GT) over time were associated with modifications of insulin secretion or sensitivity. METHODS: Plasma glucose and insulin responses to an oral GT test (OGTT) were investigated and reinvestigated 13 Years later in 14 CF patients with initial and persistent fasting euglycemia and no history of insulin treatment. Insulin sensitivity (IS) at both tests was assessed on the basis of insulin and glucose levels both in the fasting state and during OGTTs. RESULTS: From the 1st to the 2nd OGTT: (a) the prevalence of DM responses significantly increased; (b) the areas beneath the respective glucose and insulin curves significantly increased and decreased respectively; (c) IR and IS indices decreased and increased respectively, even in the patients who developed DM; (d) pulmonary function significantly worsened in the entire series, especially in the patients who developed DM. CONCLUSIONS: (i) the natural history of glyco-metabolic status in CF is characterized by deteriorating GT over time; (ii) insulinopenia plays a prominent role in the pathogenesis of GT worsening; (iii) IR does not play any significant part in the pathogenesis of DM development; (iv) deterioration of lung function tests is more severe in the subjects who develop DM over time.

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The natural history of chronic obstructive pulmonary disease

Management of Chronic Obstructive Pulmonary Disease ◽

10.1183/1025448x.00038005 ◽

2006 ◽

pp. 71-83

Author(s):

D.S. Postma ◽

H.M. Boezen

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Natural History ◽

Pulmonary Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

History Of

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Most of Staphylococcus aureus and Pseudomonas aeruginosa co-infecting isolates coexist, a condition that may impact clinical outcomes in Cystic Fibrosis patients

10.1101/2020.01.17.20017863 ◽

2020 ◽

Author(s):

Paul Briaud ◽

Sylvère Bastien ◽

Laura Camus ◽

Marie Boyadjian ◽

Philippe Reix ◽

...

Keyword(s):

Cystic Fibrosis ◽

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Multivariate Analysis ◽

Natural History ◽

Clinical Outcomes ◽

Bacterial Colonization ◽

Childhood And Adolescence ◽

History Of

AbstractStaphylococcus aureus (SA) is the major colonizer of the lung of cystic fibrosis (CF) patient during childhood and adolescence. As patient aged, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harbouring both SA and PA are frequently found in worldwide cohort. Impact of coinfection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n=112), PA only (n=48) or SA plus PA (n=52). In addition, SA and PA isolates from co-infecting patients were tested in vitro to define their interaction profile. Sixty five percent (n=34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a clinical condition less severe than others, and PA induce a poor outcome independently of the presence of SA. FEV1 is lower in patients infected by competition strain pairs than in those infected by coexisting strain pairs compared to SA mono-infection. Coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.

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La diagnosi e la gestione del prolasso rettale

Medico e Bambino ◽

10.53126/meb39453 ◽

2020 ◽

Vol 39 (7) ◽

pp. 453-457

Author(s):

Silvia Ventresca ◽

Micol Bacchini ◽

Giulia Graziani ◽

Federico Marchetti

Keyword(s):

Cystic Fibrosis ◽

Natural History ◽

Spina Bifida ◽

Rectal Prolapse ◽

Newborn Screening ◽

Complete Resolution ◽

Toilet Training ◽

Rare Occurrence ◽

The Family ◽

History Of

Rectal prolapse is an overall rare occurrence in children in the first 4 years of age. It typically tends to relapse. In the majority of cases it is not possible to highlight a single cause that determines prolapse, even if it is more frequent in children who suffer from constipation. In about 1 in 10 cases there is an underlying predisposing anatomical-neurological condition (in particular neurological: myelomenigocele, spina bifida occulta). A predisposing cause that must always be considered and excluded is cystic fibrosis, even in the age of newborn screening. Rectal prolapse management is conservative in most cases. Behavioural measures (correct toilet training, good hydration, diet rich in fibres) and the use of the macrogol laxative are fundamental. The prolapse that does not resolve spontaneously must be reduced manually by instructing the family on the technique to be used. In 90% of cases the natural history of rectal prolapse is favourable, with complete resolution within the first 4 years of age. After this age, it occurs more rarely. Surgery is rarely indicated. The current techniques that have a large consensus are sclerotherapy and laparoscopic rectopexy. The paper reports the management of recurrent rectal prolapse in a 3-year-old boy.

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The bronchodilator test in patients with airway obstruction: the responsiveness of lung function parameters

Medical alphabet ◽

10.33667/2078-5631-2021-5-57-61 ◽

2021 ◽

pp. 57-61

Author(s):

M. I. Chushkin ◽

L. A. Popova ◽

E. A. Shergina ◽

N. L. Karpina

Keyword(s):

Pulmonary Function ◽

Airway Obstruction ◽

Airway Resistance ◽

Lung Volumes ◽

Before And After ◽

Calculated Effect ◽

Volume Measurements ◽

The Difference ◽

Bronchodilator Responsiveness ◽

Chronic Airway

Interpretation of bronchodilator (BD) test based on reaction of forced expiratory in one second (FEV 1). For assessing bronchodilator responsiveness of lung volumes, airway resistance remains largely unexplored. Therefore, we assessed the response of pulmonary function parameters to BD to reveal the most responsive parameter. 90 patients with chronic airway obstruction (61 male and 29 female; aged 55±11; post- BD FEV 1 was 63.1+18.3 % predicted) performed spirometry and static lung volume measurements before and after inhalation of BD. We calculated effect size (ES) for each parameter from the difference between two means divided by the standard deviation of baseline score. There was a significant increase both FVC and FEV 1by 8.2 and 12.3 % from baseline (p<0.001). ES were 0.34 for FEV1 and 0.26 for FVC. The ES for lung volumes were from -0.07 (total lung capacity) to -0.31 (residual volume). The ES for sRtot (specific airway resistance) was -0.5 and ES for sGeff (specific effective airway conductance) was 0.95. The parameters of airway resistance and conductance were more responsive for the assessment of pulmonary function changes than spirometry and lung volumes parameters in patients with chronic airway obstruction.

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Clinical implications of the natural history of insulin secretory and sensitivity defects in cystic fibrosis

Postdoc Journal ◽

10.14304/surya.pdp.v3n11.14 ◽

2015 ◽

Author(s):

A Battezzati

Keyword(s):

Cystic Fibrosis ◽

Natural History ◽

Clinical Implications ◽

History Of

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EDNRA variants associate with smooth muscle mRNA levels, cell proliferation rates, and cystic fibrosis pulmonary disease severity

Physiological Genomics ◽

10.1152/physiolgenomics.00185.2009 ◽

2010 ◽

Vol 41 (1) ◽

pp. 71-77 ◽

Cited By ~ 18

Author(s):

Rebecca Darrah ◽

Edward McKone ◽

Clare O'Connor ◽

Christine Rodgers ◽

Alan Genatossio ◽

...

Keyword(s):

Cystic Fibrosis ◽

Cell Proliferation ◽

Smooth Muscle ◽

Pulmonary Function ◽

Smooth Muscle Cells ◽

Pulmonary Disease ◽

Muscle Cells ◽

Airway Smooth Muscle Cells ◽

Mrna Levels ◽

Protective Allele

Airway inflammation and pulmonary disease are heterogeneous phenotypes in cystic fibrosis (CF) patients, even among patients with the same cystic fibrosis transmembrane conductance regulator (CFTR) genotype. Endothelin, a proinflammatory peptide and smooth muscle agonist, is increased in CF airways, potentially contributing to the pulmonary phenotype. Four cohorts of CF patients were screened for variants in endothelin pathway genes to determine whether any of these variants associated with pulmonary function. An initial cohort of 808 CF patients homozygous for the common CF mutation, ΔF508, showed significant association for polymorphisms in the endothelin receptor A gene, EDNRA ( P = 0.04), but not in the related endothelin genes ( EDN1, EDN2, EDN3, or EDNRB) or NOS1, NOS2A, or NOS3. Variants within EDNRA were examined in three additional cohorts of CF patients, 238 patients from Seattle, WA, 303 from Ireland and the U.K., and 228 from Cleveland, OH, for a total of 1,577 CF patients. The three additional groups each demonstrated a significant association between EDNRA 3′-untranslated region (UTR) variant rs5335 and pulmonary function ( P = 0.002). At the molecular level, single nucleotide primer extension assays suggest that the effect of the variants is quantitative. EDNRA mRNA levels from cultured primary tracheal smooth muscle cells are greater for the allele that appears to be deleterious to lung function than for the protective allele, suggesting a mechanism by which increased receptor function is harmful to the CF airway. Finally, cell proliferation studies using human airway smooth muscle cells demonstrated that cells homozygous for the deleterious allele proliferate at a faster rate than those homozygous for the protective allele.

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ASTHMA IN CYSTIC FIBROSIS

Romanian Journal of Pediatrics ◽

10.37897/rjp.2015.2.2 ◽

2015 ◽

Vol 64 (2) ◽

pp. 118-121

Author(s):

Marcela Daniela Ionescu ◽

◽

Ioana-Alina Anca ◽

Mihaela Balgradean ◽

◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Airway Obstruction ◽

Autosomal Recessive ◽

Pulmonary Infection ◽

Autosomal Recessive Disease ◽

Personal History ◽

Common Symptom ◽

Infection And Inflammation ◽

History Of

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Lung disease is characterized by impaired mucocilliary clearance with airway obstruction and chronic pulmonary infection and inflammation. Wheeze is a common symptom in CF, but in some cases the wheeze is due to the presence of concomitant asthma. There is no consensus on how to define CF asthma, but the diagnosis is predominantly based on the patient’s strong family and personal history of atopy.

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