Baseline self-report 'central mechanisms' trait predicts persistent knee pain in the Knee Pain in the Community (KPIC) cohort.

OBJECTIVES: We investigated whether baseline scores for a self-report trait linked to central mechanisms predict 1 year pain outcomes in the Knee Pain in the Community cohort. METHOD: 1471 participants reported knee pain at baseline and responded to a 1-year follow-up questionnaire, of whom 204 underwent pressure pain detection thresholds (PPTs) and radiographic assessment at baseline. Logistic and linear regression models estimated the relative risks (RRs) and associations (ß) between self-report traits, PPTs and pain outcomes. Discriminative performance for each predictor was compared using receiver-operator characteristics (ROC) curves. RESULTS: Baseline Central Mechanisms trait scores predicted pain persistence (Relative Risk, RR = 2.10, P = 0.001) and persistent pain severity (ß = 0.47, P < 0.001), even after adjustment for age, sex, BMI, radiographic scores and symptom duration. Baseline joint-line PPTs also associated with pain persistence (RR range = 0.65 to 0.68, P < 0.02), but only in univariate models. Lower baseline medial joint-line PPT was associated with persistent pain severity (ß = -0.29, P = 0.013) in a fully adjusted model. The Central Mechanisms trait model showed good discrimination of pain persistence cases from resolved pain cases (Area Under the Curve, AUC = 0.70). The discrimination power of other predictors (PPTs (AUC range = 0.51 to 0.59), radiographic OA (AUC = 0.62), age, sex and BMI (AUC range = 0.51 to 0.64), improved significantly (P < 0.05) when the central mechanisms trait was included in each logistic regression model (AUC range = 0.69 to 0.74). CONCLUSION: A simple summary self-report Central Mechanisms trait score may indicate a contribution of central mechanisms to poor knee pain prognosis.

The relative efficacy of topical non-steroidal anti-inflammatory drugs and capsaicin in osteoarthritis: a network meta-analysis of randomised controlled trials.

OBJECTIVE: To compare the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) with topical capsaicin for pain relief in osteoarthritis (OA). DESIGN: A systematic literature search was conducted for randomised controlled trials (RCTs) examining any topical NSAID or capsaicin in OA. Pain relief at or nearest to 4 weeks was pooled using a random-effects network meta-analysis (NMA) in a Frequentist and Bayesian setting. Analysis was conducted for all trials and for trials using drugs listed as licensed for OA in the British National Formulary (BNF). RESULTS: The trial network comprised 28 RCTs (7372 participants), of which 17 RCTs (3174 participants) were included in the as licensed analyses. No RCTs directly compared topical NSAIDs with capsaicin. Placebo was the only common comparator for topical NSAIDs and capsaicin. Frequentist and Bayesian effect size (ES) estimates were in agreement. Topical NSAIDs were statistically superior to placebo overall (ES 0.30, 95% confidence interval [CI] 0.19 to 0.41) and as licensed (ES 0.32, 95% CI 0.24 to 0.39). However, capsaicin was only statistically superior to placebo when used at licensed doses (ES 0.41, 95% CI 0.17 to 0.64). No significant differences were observed in pain relief between topical NSAIDs and capsaicin (overall: ES 0.04, 95% CI -0.26 to 0.33; as licensed: ES-0.09, 95% CI -0.34 to 0.16). CONCLUSIONS: Current evidence indicates that topical NSAIDs and capsaicin in licensed doses may be equally effective for pain relief in OA. Whether the equivalence varies between individuals remains unknown.

Knee pain and related health in the community study (KPIC): a cohort study protocol.

BACKGROUND: The incidence, progression and related risk factors for recent-onset knee pain (KP) remain uncertain. This study aims to examine the natural history of KP including incidence and progression and to identify possible phenotypes and their associated risk factors. METHODS: A prospective community-based cohort of men and women aged 40 years or over within the East Midlands region (UK) will be recruited via a postal questionnaire from their general practices. The questionnaire will enquire about: presence and onset of KP; pain severity (0­10 numerical rating scale (NRS)); pain catastrophizing and neuropathic-like pain (NP) using the painDETECT questionnaires (definite NP scores ≥19­38); risk factors for KP and/ or osteoarthritis (OA) (age, body mass index, constitutional knee alignment, nodal OA, index: ring finger length (2D4D) ratio); quality of life (SF12); and mental health (Hospital Anxiety and Depression Scale). Clinical assessments will be undertaken in a sample of 400 participants comprising three groups: early KP (≤3 year's duration), established KP (>3 years) and no KP. Assessments will include knee radiographs (standing semi-flexed and 30(0) skyline views); knee ultrasound (synovial effusion, hypertrophy, and Doppler activity); quantitative sensory testing; muscle strength (quadriceps, hip abductor, and hand-grip); balance; gait analysis (GAITrite); and biomarker sampling. A repeat questionnaire will be sent to responders at years 1 and 3. The baseline early KP group will undergo repeat assessments at year 1 (apart from radiographs) and year 3 (with radiographs). Any incident KP individuals identified at year 1 or 3 questionnaires will have clinical and radiographic assessments at the respective time points. DISCUSSION: Baseline data will be used to examine risk factors for early onset KP and to identify KP phenotypes. Subsequent prospective data, at least to Year 3, will allow examination of the natural history of KP and risk factors for incidence and progression. TRIAL REGISTRATION: The study was registered on the clinicaltrials.gov portal: NCT02098070) on the 14th of March 2014.

Intra-population trends in the maturation and reproduction of a temperate marine herbivore Girella elevata across latitudinal clines.

Latitudinal variation in the reproductive characteristics of a temperate marine herbivore, rock blackfish Girella elevata, was examined from three regions of the south-eastern Australian coast. Biological sampling covered 780 km of coastline, including the majority of the species distribution. The sampling range incorporated three distinct oceanographic regions of the East Australian Current, a poleward-flowing western boundary current of the Southern Pacific Gyre and climate-change hotspot. Girella elevata are a highly fecund, group synchronous (multiple batch)-spawner. Mean fork length (LF ) and age at maturity were greater for females than males within all regions, with both male and female G. elevata of the southern region maturing at a greater size and age than those from the central region. Estimates of batch fecundity (FB ) were greatest in the northern and southern regions, relative to the central region where growth rates were greatest. Significant positive relationships were observed between FB and LF , and FB and total fish mass. Gonado-somatic indices indicated latitudinal synchrony in spawning seasonality between G. elevata at higher latitudes, spawning in the late austral spring and summer. A late or prolonged spawning period is evident for G. elevata from the northern region. Juvenile recruitment to intertidal rock pools within the central and southern regions was synchronous with the spawning season, however, no juveniles were found within the northern region. The implications of latitudinal variation in reproductive characteristics are discussed in the context of climate and oceanographic conditions of south-east Australia.

Osteoarthritis in the UK Armed Forces: a review of its impact, treatment and future research.

Within the UK Armed Forces, musculoskeletal injuries account for over half of all medical downgrades and discharges. Data from other Armed Forces show that osteoarthritis (OA), more common in military personnel, is likely to contribute to this, both in its primary form and following injury (post-traumatic OA, PTOA), which typically presents in the third or fourth decade. OA is not a progressive 'wear and tear' disease, as previously thought, but a heterogenous condition with multiple aetiologies and modulators, including joint damage, abnormal morphology, altered biomechanics, genetics, low-grade inflammation and dysregulated metabolism. Currently, clinical diagnosis, based on symptomatic or radiological criteria, is followed by supportive measures, including education, exercise, analgesia, potentially surgical intervention, with a particular focus on exercise rehabilitation within the UK military. Developments in OA have led to a new paradigm of organ failure, with an emphasis on early diagnosis and risk stratification, prevention strategies (primary, secondary and tertiary) and improved aetiological classification using genotypes and phenotypes to guide management, with the introduction of biological markers (biomarkers) potentially having a role in all these areas. In the UK Armed Forces, there are multiple research studies focused on OA risk factors, epidemiology, biomarkers and effectiveness of different interventions. This review aims to highlight OA, especially PTOA, as an important diagnosis to consider in serving personnel, outline current and future management options, and detail current research trends within the Defence Medical Services.

Early Pseudomonas aeruginosa predicts poorer pulmonary function in preschool children with cystic fibrosis.

BACKGROUND: We previously reported relatively normal pulmonary function (2 years of age) and computed tomography (CT, 1 year of age) in cystic fibrosis (CF) newborn screened (NBS) infants. We now report follow up of these children to preschool age. METHODS: 67 NBS children with CF and 41 healthy controls underwent pulmonary function tests in infancy (∼3 months, 1 year and 2 years) and at preschool (3-6 years). Broncho-alveolar lavage (BAL) and CT were undertaken in those with CF at 1 year. Primary outcomes at preschool were lung clearance index (LCI) and forced expired volume (FEV0.75). Risk factors for lung function impairment were identified by regression modelling, emphasising factors that could be identified or measured in the first 2 years of life. RESULTS: At preschool age children with CF had poorer lung function than controls, mean(95% CI) difference in LCI z-score: 1.47(0.96;1.97) and FEV0.75 z-score -0.54(-0.98; -0.10). Isolation of Pseudomonas aeruginosa before 6 months was a highly significant predictor of raised (abnormal) preschool LCI, associated with a mean (95%CI) increase of 1.69(0.43, 2.95) z-scores, compared to those with no Pseudomonas aeruginosa during the first 2 years of life. Including 2 year LCI and 1 year CT data in the predictive model increased the r2 from 13% to 61%. CONCLUSIONS: Lung function deteriorates after 2 years in NBS children with CF. Isolation of Pseudomonas aeruginosa before 6 months and minor abnormalities of infant lung function tests and CT in infancy are associated with higher preschool LCI.

Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age.

Advances in neonatal care have resulted in increased survival of children born extremely pre-term (EP). Nevertheless the incidence of bronchopulmonary dysplasia and long-term respiratory morbidity remains high. We investigated the nature of pathophysiological changes at 11 yrs of age to ascertain whether respiratory morbidity in EP children primarily reflects alterations in the lung periphery or more centralised airway function in this population. Spirometry, plethysmography, diffusing capacity, exhaled nitric oxide, multiple-breath washout, skin tests and methacholine challenge were used during laboratory-based assessments in a subgroup of the 1995 EPICure cohort and in controls. Results were obtained in 49 EP and 52 control children. Lung function abnormalities were found in 78% of EP children, with evidence of airway obstruction, ventilation inhomogeneity, gas trapping and airway hyperresponsiveness. Levels of atopy and exhaled nitric oxide were similar between the groups. Prior wheeze was associated with significant reductions in forced flows and volumes. By contrast, abnormalities of the lung periphery appear to be mediated primarily through EP birth per se. The prevalence of lung function abnormalities, which is largely obstructive in nature and likely to have long-term implications, remains high among 11-yr-old children born EP. Spirometry proved an effective means of detecting these persistent abnormalities.

Influence of secular trends and sample size on reference equations for lung function tests.

The aim of our study was to determine the contribution of secular trends and sample size to lung function reference equations, and establish the number of local subjects required to validate published reference values. 30 spirometry datasets collected between 1978 and 2009 provided data on healthy, white subjects: 19,291 males and 23,741 females aged 2.5-95 yrs. The best fit for forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC as functions of age, height and sex were derived from the entire dataset using GAMLSS. Mean z-scores were calculated for individual datasets to determine inter-centre differences. This was repeated by subdividing one large dataset (3,683 males and 4,759 females) into 36 smaller subsets (comprising 18-227 individuals) to preclude differences due to population/technique. No secular trends were observed and differences between datasets comprising >1,000 subjects were small (maximum difference in FEV(1) and FVC from overall mean: 0.30- -0.22 z-scores). Subdividing one large dataset into smaller subsets reproduced the above sample size-related differences and revealed that at least 150 males and 150 females would be necessary to validate reference values to avoid spurious differences due to sampling error. Use of local controls to validate reference equations will rarely be practical due to the numbers required. Reference equations derived from large or collated datasets are recommended.

Increasing adherence with the use of hip protectors for older people living in the community.

UNLABELLED: For people at high risk of hip fracture living in community settings, providing hip protectors at no cost increased adherence, but the additional effect of an educational programme was limited. Overall, the level of adherence was modest. INTRODUCTION: The objective of the study was to increase adherence with hip protector use by older people at high risk of hip fracture. The study included two randomised controlled trials with 308 older people recruited from three hospital rehabilitation wards and 171 older people recruited from the community. METHODS: Participants were randomised into three groups. The control group received a brochure about hip protectors. The no cost group were fitted with free hip protectors and asked to use them. The combined group received free hip protectors and education sessions about their use. Adherence with the use of hip protectors at 3 and 6 months after recruitment was measured. Secondary outcomes were falls, fractures and hospitalisations. RESULTS: Very few participants in the two control groups bought a hip protector. Overall adherence in the four intervention groups was modest, but higher in the community recruitment setting (49%) than in the hospital recruitment setting (36%) at 6 months. In the community recruitment group, at 3 months of follow-up, a significantly higher number of participants in the combined group (62%) were wearing hip protectors compared to the no cost group (43%, p=0.04). Five hip fractures occurred during the study, with four sustained whilst not wearing the hip protectors. CONCLUSION: Providing hip protectors at no cost to community living older people at high risk of hip fractures modestly increases initial acceptance and adherence with hip protector use. Additional education may further increase hip protector use in people living in the community in the short term.

Reference values for lung function: past, present and future.

Reliable interpretation of pulmonary function results relies on the availability of appropriate reference data to help distinguish between health and disease and to assess the severity and nature of any functional impairment. The overwhelming number of published reference equations, with at least 15 published for spirometry alone in the past 3 yrs, complicates the selection of an appropriate reference. The use of inappropriate reference equations and misinterpretation, even when potentially appropriate equations are used, can lead to serious errors in both under and over diagnosis, with its associated burden in terms of financial and human costs. Further misdiagnosis occurs when fixed cut-offs, such as 80% predicted forced expiratory volume in 1 s (FEV(1)) or 0.70 FEV(1)/forced vital capacity, are used; particularly in young children and elderly adults. While per cent predicted has historically been used to interpret lung function results, z-scores are more appropriate as they take into account the predicted value, as well as the between-subject variability of measurements. We aim to highlight some of the main issues in selecting and using reference equations and discuss how recent developments may improve interpretation of pulmonary function results.

Reference ranges for interrupter resistance technique: the Asthma UK Initiative.

Measuring interrupter resistance (R(int)) is an increasingly popular lung function technique and especially suitable for preschool children because it is simple, quick and requires only passive cooperation. A European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force recently published empirical recommendations related to procedures, limitations and interpretation of the technique. However, for valid interpretation, high-quality reference equations are required and these have been lacking. The aim of the present study was to collate R(int) data from healthy children in order to produce more robust reference equations. A further aim was to examine the influence of methodological differences on predicted R(int) values. R(int) data from healthy children were collected from published and unpublished sources. Reference equations for expiratory and inspiratory R(int) were developed using the LMS (lambda, mu, sigma) method. Data from 1,090 children (51% males) aged 3-13 yrs were collated to construct sex-specific reference equations for expiratory R(int) and data from 629 children (51% males) were collated for inspiratory R(int). Height was the best independent predictor of both expiratory and inspiratory R(int). Differences between centres were clinically irrelevant, and differences between ethnic groups could not be examined. The availability of a large and generalisable sample and the use of modern statistical techniques enabled the development of more appropriate reference equations for R(int) in young children.

Reference equations for specific airway resistance in children: the Asthma UK initiative.

Plethysmographic specific airway resistance (sR(aw)) is a useful research method for discriminating lung disease in young children. Its use in clinical management has, however, been limited by lack of consensus regarding equipment, methodology and reference data. The aim of our study was to collate reference data from healthy children (3-10 yrs), document methodological differences, explore the impact of these differences and construct reference equations from the collated dataset. Centres were approached to contribute sR(aw) data as part of the Asthma UK initiative. A random selection of pressure-flow plots were assessed for quality and site visits elucidated data collection and analysis protocols. Five centres contributed 2,872 measurements. Marked variation in methodology and analysis excluded two centres. sR(aw) over-read sheets were developed for quality control. Reference equations and recommendations for recording and reporting both specific effective and total airway resistance (sR(eff) and sR(tot), respectively) were developed for White European children from 1,908 measurements made under similar conditions. Reference sR(aw) data collected from a single centre may be misleading, as methodological differences exist between centres. These preliminary reference equations can only be applied under similar measurement conditions. Given the potential clinical usefulness of sR(aw), particularly with respect to sR(eff), methodological guidelines need to be established and used in prospective data collection.

Changes in the FEV1/FVC ratio during childhood and adolescence: an intercontinental study.

In children, the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) is reportedly constant or falls linearly with age, whereas the ratio of residual volume (RV) to total lung capacity (TLC) remains constant. This seems counter-intuitive given the changes in airway properties, body proportions, thoracic shape and respiratory muscle function that occur during growth. The age dependence of lung volumes, FEV1/FVC and RV/TLC were studied in children worldwide. Spirometric data were available for 22,412 healthy youths (51.4% male) aged 4-20 yrs from 15 centres, and RV and TLC data for 2,253 youths (56.7% male) from four centres; three sets included sitting height (SH). Data were fitted as a function of age, height and SH. In childhood, FVC outgrows TLC and FEV1, leading to falls in FEV1/FVC and RV/TLC; these trends are reversed in adolescence. Taking into account SH materially reduces differences in pulmonary function within and between ethnic groups. The highest FEV1/FVC ratios occur in those shortest for their age. When interpreting lung function test results, the changing pattern in FEV1/FVC and RV/TLC should be considered. Prediction equations for children and adolescents should take into account sex, height, age, ethnic group, and, ideally, also SH.

Heritability of lung function in severe alpha-1 antitrypsin deficiency.

Severe alpha-1 antitrypsin (AAT) deficiency is a proven genetic risk factor for COPD, but there is marked variation in the development of COPD among AAT deficient subjects. To investigate familial aggregation of lung function in subjects with AAT deficiency, we estimated heritability for forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) in 378 AAT deficient subjects from 167 families in the AAT Genetic Modifiers Study; all subjects were verified homozygous for the Z AAT deficiency allele. Heritability was evaluated for models that included and excluded an ascertainment correction, as well as for models that excluded, included and were stratified by a cigarette smoking covariate. In models without an ascertainment correction, and in all models without a covariate for smoking, no evidence for familial aggregation of lung function was observed. In models conditioned on the index proband with covariates for smoking, post-bronchodilator FEV1/FVC demonstrated significant heritability (0.26 +/- 0.14, p = 0.03). When we limited the analysis to subjects with a smoking history, post-bronchodilator FEV1 demonstrated significant heritability (0.47 +/- 0.21, p = 0.02). Severity rate phenotypes were also assessed as potential phenotypes for genetic modifier studies. Significant heritability was found with all age-of-onset threshold models that included smoking and ascertainment adjustments. Using the t-distribution, the heritability estimates ranged from 0.43 to 0.64, depending on the age-of-onset of FEV1 decline used for the severity rate calculation. Correction for ascertainment and consideration of gene-by-smoking interactions will be crucial for the identification of genes that may modify susceptibility for COPD in families with AAT deficiency.

Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency is a genetic condition associated with severe, early-onset chronic obstructive pulmonary disease (COPD). However, there is significant variability in lung function impairment among persons with the protease inhibitor ZZ genotype. Early identification of persons at highest risk of developing lung disease could be beneficial in guiding monitoring and treatment decisions. Using a multicenter, family-based study sample (2002-2005) of 372 persons with the protease inhibitor ZZ genotype, the authors developed prediction models for forced expiratory volume in 1 second (FEV(1)) and the presence of severe COPD using demographic, clinical, and genetic variables. Half of the data sample was used for model development, and the other half was used for model validation. In the training sample, variables found to be predictive of both FEV(1) and severe COPD were age, sex, pack-years of smoking, bronchodilator responsiveness, chronic bronchitis symptoms, and index case status. In the validation sample, the predictive model for FEV(1) explained 50% of the variance in FEV(1), and the model for severe COPD exhibited excellent discrimination (c statistic = 0.88).

Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study.

BACKGROUND: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth. METHODS: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling. RESULTS: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes. CONCLUSION: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.

Lung function and clinical risk factors for asthma in infants and young children with recurrent wheeze.

BACKGROUND: Although several risk factors for asthma have been identified in infants and young children with recurrent wheeze, the relevance of assessing lung function in this group remains unclear. Whether lung function is reduced during the first 2 years in recurrently wheezy children, with and without clinical risk factors for developing subsequent asthma (ie, parental asthma, personal history of allergic rhinitis, wheezing without colds and/or eosinophil level >4%) compared with healthy controls was assessed in this study. METHODS: Forced expiratory flows and volumes in steroid naïve young children with >or=3 episodes of physician confirmed wheeze and healthy controls, aged 8-20 months, were measured using the tidal and raised volume rapid thoracoabdominal compression manoeuvres. RESULTS: Technically acceptable results were obtained in 50 wheezy children and 30 controls using tidal rapid thoracoabdominal compression, and 44 wheezy children and 29 controls with the raised volume technique. After adjustment for sex, age, body length at test and maternal smoking, significant reductions in z scores for forced expiratory volume at 0.5 s (mean difference (95% CI) -1.0 (-1.5 to -0.5)), forced expired flow after 75% forced vital capacity (FVC) has been exhaled (FEF(25)) (-0.6 (-1.0 to -0.2)) and average forced expired flow over the mid 50% of FVC (FEF(25-75)) (-0.8 (-1.2 to -0.4)) were observed in those with recurrent wheeze compared with controls. Wheezy children with risk factors for asthma (n = 15) had significantly lower z scores for FVC (-0.7 (-1.4 to -0.04)) and FEF(25-75) (-0.6 (-1.2 to -0.1)) than those without such risk factors (n = 29). CONCLUSIONS: Compared with healthy controls, airway function is reduced in young children with recurrent wheeze, particularly those at risk for subsequent asthma. These findings provide further evidence for associations between clinical risk factors and impaired respiratory function in early life.

Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction.

AIM: The prevalence of airway obstruction varies widely with the definition used. OBJECTIVES: To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. METHODS: We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) and its lower limit of normal (LLN) from the literature. FEV(1)/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17-90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV(1)/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. RESULTS: The LLN for FEV(1)/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995-1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17-45% of men and 7-26% of women for GOLD; 0-18% of men and 0-16% of women for ATS/ERS; and 0-9% of men and 0-11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. CONCLUSIONS: Airway obstruction should be defined by FEV(1)/FVC and FEV(1) being below the LLN using appropriate reference equations.

Wireless capsule endoscopy in the investigation of intestinal Behçet's syndrome.

OBJECTIVE: Intestinal Behçet's Syndrome (BS) is a difficult diagnosis to establish. We describe the use of wireless capsule endoscopy (WCE) in the investigation of 11 patients with suspected intestinal BS. METHODS: Out of 11 patients, 10 with suspected intestinal BS were found to have small intestinal ulcers on capsule endoscopy. Each case was retrospectively assessed for symptoms, signs, anaemia, other investigations, treatment and complications. RESULTS: All 11 patients had established diagnoses of BS as defined by the International Study Group criteria. Central abdominal pain and change in bowel habit were the predominant symptoms, both occurring in seven patients. Upper gastrointestinal (GI) endoscopy and colonoscopy identified duodenitis, ileitis and colitis in three patients. Barium studies and CT were normal in all cases. WCE revealed small intestinal ulcers throughout the ileum in five patients and ulcers located either in the proximal and/or distal ileum in five other patients. One patient had significant symptoms, signs and ulcers leading to a change in treatment to infliximab, and this resulted in resolution of symptoms and ulcers. Ten age- and sex-matched controls investigated for unexplained GI symptoms had no intestinal lesions on capsule endoscopy. CONCLUSION: WCE is useful in the investigation of GI symptoms in BS. It is particularly helpful in those patients in whom conventional investigations have been normal or fail to account for symptoms and signs. This technique may guide treatment and provide a better understanding of intestinal pathology in BS.

Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosus.

BACKGROUND: Lichen amyloidosus is a localized, chronic, pruritic skin disease characterized by deposition of amyloid in the papillary dermis. The pathogenesis of the pruritus of lichen amyloidosus is largely unknown. OBJECTIVES: To determine any change in the nerve fibre density in lichen amyloidosus lesions as an explanation for itch. METHODS: Using an antibody to protein gene product (PGP) 9.5, the immunohistochemical analysis of the skin biopsies of 30 Hispanic patients with clinicopathologically proven lichen amyloidosus and of 11 healthy Hispanic controls matched for age, sex and site was performed. RESULTS: Unexpectedly, the mean amount of PGP9.5 stain, a measure for nerve fibre amount, for the healthy controls was higher than the lichen amyloidosus group both in the epidermis (P < 0.0019) and dermoepidermal junction (P < 0.0064). No change was observed in the papillary dermis. Furthermore, the proportion of area covered by PGP9.5 showed a significant decrease in the epidermis (P < 0.0024) and dermoepidermal junction (P < 0.0075) in lichen amyloidosus compared with healthy controls. Age, gender and body site were found not to be influencing factors in nerve fibre amounts in lichen amyloidosus samples. CONCLUSIONS: We speculate that the severe pruritus observed in lichen amyloidosus might be the result of the hypersensitivity of the remaining nerve fibres as a response to an unexplained neurodegeneration of the absent nerve fibres.