Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
1.
Respirol Case Rep ; 11(1): e01079, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36569635

ABSTRACT

Diagnosis and management of CRMS/CFSPID and cystic fibrosis (CF) with mild phenotypes remains challenging, and this extends to expanding practice with the use of CFTR modulators. We describe a case of an 18-year-old man with p.F508del/p.Arg117His(7T) initially presenting with CRMS/CFSPID. He went on to be diagnosed with pancreatic sufficient CF with minimal lung disease. However, he has had significant CFTR-related symptoms with recurrent pancreatitis and chronic sinusitis. These non-pulmonary symptoms resolved following introduction of the CFTR modulator ivacaftor. Care for those with mild CF phenotypes, CRMS/CFSPID and those with CFTR-RD must be individualized, and open dialogue, education and patient centred care is necessary to ascertaining which patients might benefit from management in a multidisciplinary CF clinic and treatment. There may be a role for expanding the use of CFTR modulators to include non-pulmonary manifestations of CFTR dysfunction in some cases.

2.
J Neuromuscul Dis ; 8(1): 53-61, 2021.
Article in English | MEDLINE | ID: mdl-32925088

ABSTRACT

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.


Subject(s)
Amyotrophic Lateral Sclerosis , Muscular Atrophy, Spinal , Muscular Dystrophies, Limb-Girdle , Muscular Dystrophy, Duchenne , Myotonic Dystrophy , Registries , Adolescent , Adult , Aged , Aged, 80 and over , Canada , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult
3.
Eur Respir J ; 55(4)2020 04.
Article in English | MEDLINE | ID: mdl-31949117

ABSTRACT

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.


Subject(s)
Cystic Fibrosis , Adolescent , Australia , Child , Child, Preschool , Disease Progression , Follow-Up Studies , Humans , Lung/diagnostic imaging , New Zealand
6.
Genet Med ; 20(11): 1485, 2018 11.
Article in English | MEDLINE | ID: mdl-29388943

ABSTRACT

Zoe McDonald, BSc, was omitted from the list of article coauthors. Her name should have been included as the seventh author, following Clare Elizabeth Hunt. Her affiliation is Victorian Clinical Genetics Services, Parkville, Victoria, Australia. The authors regret the error.

7.
Genet Med ; 20(5): 513-523, 2018 04.
Article in English | MEDLINE | ID: mdl-29261177

ABSTRACT

PurposeTo describe our experience of offering simultaneous genetic carrier screening for cystic fibrosis (CF), fragile X syndrome (FXS), and spinal muscular atrophy (SMA).MethodsCarrier screening is offered through general practice, obstetrics, fertility, and genetics settings before or in early pregnancy. Carriers are offered genetic counseling with prenatal/preimplantation genetic diagnosis available to those at increased risk.ResultsScreening of 12,000 individuals revealed 610 carriers (5.08%; 1 in 20): 342 CF, 35 FXS, 241 SMA (8 carriers of 2 conditions), approximately 88% of whom had no family history. At least 94% of CF and SMA carriers' partners were tested. Fifty couples (0.42%; 1 in 240) were at increased risk of having a child with one of the conditions (14 CF, 35 FXS, and 1 SMA) with 32 pregnant at the time of testing. Of these, 26 opted for prenatal diagnosis revealing 7 pregnancies affected (4 CF, 2 FXS, 1 SMA).ConclusionThe combined affected pregnancy rate is comparable to the population risk for Down syndrome, emphasizing the need to routinely offer carrier screening. The availability of appropriate genetic counseling support and a collaborative approach between laboratory teams, genetics services, health professionals offering screening, and support organizations is essential.


Subject(s)
Cystic Fibrosis/epidemiology , Cystic Fibrosis/genetics , Fragile X Syndrome/epidemiology , Fragile X Syndrome/genetics , Genetic Carrier Screening , Muscular Atrophy, Spinal/epidemiology , Muscular Atrophy, Spinal/genetics , Adult , Australia/epidemiology , Cystic Fibrosis/diagnosis , Female , Fragile X Syndrome/diagnosis , Gene Frequency , Genetic Carrier Screening/methods , Genetic Testing , Humans , Male , Mass Screening , Middle Aged , Muscular Atrophy, Spinal/diagnosis , Pregnancy , Prenatal Diagnosis , Prevalence , Young Adult
8.
Med J Aust ; 205(11): 527, 2016 Dec 12.
Article in English | MEDLINE | ID: mdl-27927152
9.
Clin Chem Lab Med ; 54(4): 561-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26457780

ABSTRACT

BACKGROUND: The aim of the study was to develop a method for sweat chloride (Cl) quantification using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to present to the Joint Committee for Traceability in Laboratory Medicine (JCTLM) as a candidate reference method for the diagnosis of cystic fibrosis (CF). METHODS: Calibration standards were prepared from sodium chloride (NaCl) to cover the expected range of sweat Cl values. Germanium (Ge) and scandium (Sc) were selected as on-line (instrument based) internal standards (IS) and gallium (Ga) as the off-line (sample based) IS. The method was validated through linearity, accuracy and imprecision studies as well as enrolment into the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) for sweat electrolyte testing. RESULTS: Two variations of the ICP-MS method were developed, an on-line and off-line IS, and compared. Linearity was determined up to 225 mmol/L with a limit of quantitation of 7.4 mmol/L. The off-line IS demonstrated increased accuracy through the RCPAQAP performance assessment (CV of 1.9%, bias of 1.5 mmol/L) in comparison to the on-line IS (CV of 8.0%, bias of 3.8 mmol/L). Paired t-tests confirmed no significant differences between sample means of the two IS methods (p=0.53) or from each method against the RCPAQAP target values (p=0.08 and p=0.29). CONCLUSIONS: Both on and off-line IS methods generated highly reproducible results and excellent linear comparison to the RCPAQAP target results. ICP-MS is a highly accurate method with a low limit of quantitation for sweat Cl analysis and should be recognised as a candidate reference method for the monitoring and diagnosis of CF. Laboratories that currently practice sweat Cl analysis using ICP-MS should include an off-line IS to help negate any pre-analytical errors.


Subject(s)
Chlorides/analysis , Cystic Fibrosis/diagnosis , Mass Spectrometry/methods , Mass Spectrometry/standards , Sweat/chemistry , Calibration , Humans
10.
Med J Aust ; 203(11): 436, 2015 Dec 14.
Article in English | MEDLINE | ID: mdl-26654609
11.
Pediatr Pulmonol ; 50(10): 947-54, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25200397

ABSTRACT

RATIONALE: To determine whether spirometry and regular medical review improved quality of life or other outcomes in children and adolescents with asthma. METHODS: We conducted two cluster randomized controlled trials. We recruited 238 asthma patients aged between 7 and 17 years from 56 general practices in South Eastern Australia. Participants were randomized to receive an intervention that included spirometry or usual care. The main outcome measure was asthma related quality of life. RESULTS: Baseline characteristics were well matched between the intervention and control groups. Neither trial found any difference in asthma related quality of life between groups. However because of measurement properties, a formal meta-analysis could not be performed. Nor were there any significant effects of the intervention upon asthma attacks, limitation to usual activities, nocturnal cough, bother during physical activity, worry about asthma, or written asthma action plans. CONCLUSIONS: The findings do not support more widespread use of spirometry for the management of childhood asthma in general practice, unless it is integrated into a complete management model.


Subject(s)
Asthma/therapy , Continuity of Patient Care , Quality of Life , Spirometry , Adolescent , Australia , Child , Disease Management , Female , Forced Expiratory Volume , General Practice , Humans , Male , Medication Adherence
12.
Pediatr Pulmonol ; 49(2): 106-17, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24249707

ABSTRACT

The sweat test remains important as a diagnostic test for cystic fibrosis (CF) and has contributed greatly to our understanding of CF as a disease of epithelial electrolyte transport. The standardization of the sweat test, by Gibson and Cooke [Gibson and Cooke (1959) Pediatrics 1959;23:5], followed observations of excessive dehydration amongst patients with CF and confirmed the utility as a diagnostic test. Quantitative pilocarpine iontophoresis remains the gold standard for sweat induction, but there are a number of collection and analytical methods. The pathophysiology of electrolyte transport in sweat was described by Quinton [Quinton (1983) Nature 1983;301:421-422], and this complemented the developments in genetics that discovered the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial-based electrolyte transport protein. Knowledge of CF has since increased rapidly and further developments in sweat testing include: new collection methods, further standardization of the technique with international recommendations and age related reference intervals. More recently, sweat chloride values have been used as proof of effect for the new drugs that activate CFTR. However, there remain issues with adherence to sweat test guidelines in many countries and there are gaps in our knowledge, including reference intervals for some age groups and stability of sweat samples in transport. Furthermore, modern methods of elemental quantification need to be explored as alternatives to the original analytical methods for sweat electrolyte measurement. The purpose of this review is therefore to describe the development of the sweat test and consider future directions.


Subject(s)
Chlorides/metabolism , Cystic Fibrosis/diagnosis , Sweat/metabolism , Biomarkers/metabolism , Clinical Chemistry Tests/methods , Clinical Chemistry Tests/standards , Clinical Chemistry Tests/trends , Cystic Fibrosis/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Hot Temperature , Humans , New York , Practice Guidelines as Topic , Reference Values , Specimen Handling
13.
Neurology ; 78(10): 702-8, 2012 Mar 06.
Article in English | MEDLINE | ID: mdl-22357716

ABSTRACT

OBJECTIVES: Autonomic deficits in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite Autonomic Severity Score (CASS) is a validated instrument for laboratory quantitation of autonomic failure derived from standard autonomic reflex tests. We characterized dysautonomia in CIDP using CASS. METHODS: Autonomic function was retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0 (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3), cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic deficits was measured with Neuropathy Impairment Score (NIS). Degree of small fiber involvement was assessed with quantitative sensation testing. Thermoregulatory sweat test (TST) was available in 8 patients. RESULTS: Patients (25 men) were middle-aged (45.0 ± 14.9 years) with longstanding CIDP (3.5 ± 4.3 years) of moderate severity (NIS, 46.5 ± 32.7). Autonomic symptoms were uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%). Autonomic deficits (CASS ≥1) were frequent (22/47; 47%) but very mild (CASS, 0.8 ± 0.9; CASS ≤3, all cases). Deficits were predominantly sudomotor (16/47; 34%) and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was predominantly distal and postganglionic. Somatic deficits (disease duration, severity, small fiber deficits) did not predict presence of autonomic deficits. CONCLUSION: Our data characterize the autonomic involvement in classic CIDP as mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at the distal postganglionic axon. Extensive or severe autonomic involvement (CASS ≥4) in suspected CIDP should raise concern for an alternative diagnosis.


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Autonomic Nervous System/physiopathology , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/physiopathology , Adult , Body Temperature Regulation/physiology , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Severity of Illness Index , Sweating/physiology
14.
Med J Aust ; 196(1): 67-70, 2012 Jan 16.
Article in English | MEDLINE | ID: mdl-22256939

ABSTRACT

OBJECTIVE: To compare three cystic fibrosis (CF) newborn screening strategies used in Victoria since 1989. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of newborn screening and clinical records for people with CF born in Victoria between 1989 and 2008 to compare screening strategies: repeat immunoreactive trypsinogen (IRT) testing (IRT/IRT, 1989-1990), IRT and p.F508del mutation analysis (IRT/p.F508del, 1991-2006) and IRT with analysis of 12 CFTR mutations (IRT/12 mutations, 2007-2008). MAIN OUTCOME MEASURES: Total number of infants screened, people identified with CF (by screening or clinical diagnosis), number of CF-affected terminations of pregnancy, and number of carriers detected. RESULTS: There were 420 people born with CF (live-birth prevalence, 1/3139; 95% CI, 1/2853-1/3462) and 78 CF-affected pregnancy terminations (overall prevalence, 1/2647; 95% CI, 1/2425-1/2896). Of the babies born with CF, 283 (67.4%) were detected by newborn screening alone, 61 (14.5%) had meconium ileus, 33 (7.9%) had a family history of CF, nine (2.1%) were diagnosed antenatally, and 34 (8.1%) were missed by screening (17 missed because IRT level was < 99th percentile, two with repeat IRT level not elevated, 14 without a screened CFTR mutation, and one with missing data). The sensitivities of the protocols were 86.6% for IRT/IRT, 89.9% for IRT/p.F508del, and 95.8% for IRT/12 mutations. Including 12 mutations in the analysis detected one patient who would otherwise have been missed and, had this protocol been implemented from 1989, it would have detected four others. CONCLUSION: Most babies with CF without meconium ileus, a family history or antenatal diagnosis are detected by newborn screening. Despite improved sensitivity with the 12-mutation analysis, most infants detected would have been diagnosed using the IRT/p.F508del protocol.


Subject(s)
Cystic Fibrosis/epidemiology , Genetic Testing/methods , Neonatal Screening/methods , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , DNA/analysis , DNA/genetics , DNA Mutational Analysis , Female , Follow-Up Studies , Humans , Infant, Newborn , Male , Mutation , Pregnancy , Prevalence , Prognosis , Retrospective Studies , Sweat/chemistry , Time Factors , Trypsinogen/genetics , Victoria/epidemiology
17.
Med J Aust ; 193(3): 157-60, 2010 Aug 02.
Article in English | MEDLINE | ID: mdl-20678044

ABSTRACT

Cystic fibrosis (CF) carrier testing can be used to inform reproductive decision making, allowing carriers to avoid having a child with CF. A government-funded, population-based CF carrier screening program would allow greater equity of access to this test. The setting in which CF carrier screening is offered significantly affects the extent to which participants make well informed, voluntary decisions to accept or decline testing. Screening offered before pregnancy and in non-clinical environments better promotes participant autonomy than screening offered in the prenatal consultation.


Subject(s)
Cystic Fibrosis/genetics , Ethics, Medical , Genetic Carrier Screening/methods , Choice Behavior , Cystic Fibrosis/prevention & control , Female , Genetic Counseling , Genetic Testing , Humans , Models, Theoretical , Pregnancy , Prenatal Diagnosis
18.
Eur J Hum Genet ; 18(10): 1084-9, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20512163

ABSTRACT

Newborn screening (NBS) for cystic fibrosis (CF) provides the opportunity for cascade carrier testing of relatives. Uptake of testing by adult non-parent relatives of children diagnosed with CF through NBS has not been previously described, and this study describes uptake by both parents and adult non-parent relatives in Victoria, Australia. Pedigrees were taken from parents of children who were born in 2000-2004 and diagnosed with CF. A total of 40 families were eligible for the study and 30 (75%) were recruited. In all, 716 non-parent relatives were identified from the pedigrees as eligible for carrier testing, and 82 (adjusted uptake percentage: 11.8%; 95% confidence interval 8.0-15.7) have had carrier testing by March 2009. On average, 2.7 non-parent relatives per family had CF carrier testing after diagnosis through NBS. The odds of being tested were greater for females than males (adjusted odds ratio 1.61; 95% confidence interval 1.11-2.33; P=0.01) and greater for those more closely related to the child with CF (adjusted odds ratio 5.17; 95% confidence interval 2.38-11.24; P<0.001). Most relatives who undergo testing are tested immediately after the baby's diagnosis; however, some testing is undertaken up to 8 years later. These results indicate that in a clinical setting, the diagnosis of a baby with CF by NBS does not lead to carrier testing for the majority of the baby's non-parent relatives. We suggest re-contact with parents to offer cascade carrier testing.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Family , Genetic Carrier Screening , Genetic Testing , Neonatal Screening , Adult , Attitude to Health , Australia , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Cystic Fibrosis/prevention & control , Data Collection , Data Interpretation, Statistical , Dystonic Disorders/diagnosis , Dystonic Disorders/prevention & control , Female , Genetic Counseling , Humans , Infant, Newborn , Life Expectancy , Male , Parents , Pedigree
19.
Med J Aust ; 190(5): 262-4, 2009 Mar 02.
Article in English | MEDLINE | ID: mdl-19296792

ABSTRACT

A previously well 2-year-old girl presented with acute respiratory distress. After multiple investigations she was diagnosed with spontaneous chylothorax, attributed to strenuous vomiting. To our knowledge, this is the second reported case of spontaneous chylothorax occurring after the neonatal period.


Subject(s)
Chylothorax/etiology , Thoracic Duct/injuries , Vomiting/complications , Child, Preschool , Chylothorax/surgery , Female , Humans , Rupture , Thoracic Surgery, Video-Assisted
20.
Med J Aust ; 189(10): 578-82, 2008 Nov 17.
Article in English | MEDLINE | ID: mdl-19012558

ABSTRACT

Chronic neonatal lung disease (CNLD) is defined as a supplemental oxygen requirement beyond 36 weeks' postmenstrual age, with more severely affected infants requiring oxygen beyond a full-term-equivalent age. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who develop hypoxia in air. There is a lack of data on the most appropriate minimum mean target oxygen saturation (Spo(2)) level. Reflecting a variety of clinical practices and infant comorbidities (frequency of oxygen desaturation, presence of pulmonary hypertension, retinopathy of prematurity, and adequacy of growth), the minimum mean target range for Spo(2) during overnight oximetry should be 93%-95%. The effect of supplemental oxygen on carbon dioxide retention should be considered before deciding on an oxygen flow. Most infants with CNLD are not ready for discharge until their supplemental oxygen requirement is < or = 0.5 litres per minute delivered through a nasal cannula. The safety of short-term disconnection from supplemental oxygen should be assessed before discharge. Assessment of oxygenation during sleep with continuous overnight oximetry or polysomnography is recommended when weaning infants from supplemental oxygen. Discontinuation of oxygen therapy is based on clinical assessments and documentation of adequate oxygenation in room air. There is limited objective evidence on which to base recommendations.


Subject(s)
Home Care Services , Infant, Premature, Diseases/therapy , Lung Diseases/therapy , Oxygen Inhalation Therapy , Australia , Chronic Disease , Humans , Infant , Infant, Newborn , Infant, Premature , New Zealand
SELECTION OF CITATIONS
SEARCH DETAIL
...