Atypical facial presentation of subcutaneous fat necrosis of the newborn.

Subcutaneous fat necrosis of the newborn (SCFN) is a rare self-limiting panniculitis. It is thought to be associated with perinatal hypoxia and therapeutic hypothermia. It is characterised by firm subcutaneous nodules on the back, shoulder and arms. We present a rare facial presentation of SCFN in a 4-week-old infant with no history of therapeutic cooling. She presented with a discrete right cheek mass with no overlying skin changes. We present the diagnostic challenge and undertake a review of the literature. SCFN is an important differential diagnosis in a neonate with subcutaneous facial lesions. SCFN can be complicated by metabolic derangements including hypercalcaemia.

The PEARL score predicts 90-day readmission or death after hospitalisation for acute exacerbation of COPD.

BACKGROUND: One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. METHODS: In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. RESULTS: Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. CONCLUSIONS: The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.

Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD.

BACKGROUND: Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. METHODS: The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identified by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. RESULTS: In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. CONCLUSIONS: DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.

The presentation and natural history of asbestos-induced diffuse pleural thickening.

BACKGROUND: Three forms of asbestos-related benign pleural disease are recognized: discrete pleural plaques, pleural effusions and diffuse pleural fibrosis. Of these, diffuse pleural fibrosis is the most significant on account of its chronicity and associated morbidity. AIMS: The objectives of this study were to determine the latency of asbestos-induced diffuse pleural fibrosis, its presenting features and its clinical course once established. METHODS: We conducted a retrospective review of 75 patients with asbestos-induced diffuse pleural fibrosis referred for assessment at our institution from 1992 to 2007. Diffuse pleural fibrosis was considered to be present if there was obliteration of the costophrenic angle in continuity with at least 3-mm pleural thickening, in accordance with the International Labour Organization 2000 Classification. RESULTS: The median latency for development of diffuse pleural fibrosis from first asbestos exposure was 34 years. Seventy-three per cent of patients had unilateral disease at presentation and 24% of these were observed to develop contralateral disease after a median of 2 years. Unilateral pleural disease was commonest on the right. Forty per cent of patients presented with pleural effusions preceding the development of diffuse pleural thickening. The median latency for development of pleural effusions from onset of exposures was 38 years. Eighty per cent of the pleural effusions were unilateral. Once established, pleural thickening was reported to have remained stable in 91% on the ipsilateral side. CONCLUSIONS: The findings of this study may help in providing further insight into the natural history of diffuse pleural fibrosis to guide the clinician in the management of this condition.

Insulin-like growth factor binding protein-1 in PCOS: a systematic review and meta-analysis.

BACKGROUND: Despite extensive research, the pathogenesis of polycystic ovary syndrome (PCOS) remains unclear. Putatively, an elevated circulating concentration of insulin inhibits the production of insulin-like growth factor binding protein-1 (IGFBP-1), thus increasing the level of free IGF-I in serum and stimulating ovarian androgen production. Decreased IGFBP-1 has been reported in PCOS and in obesity; however, there are inconsistencies in the evidence. This systematic review and meta-analysis aimed to determine whether IGFBP-1 is decreased in PCOS when controlling for the influence of BMI. METHODS: Articles published between 1988 and 2008 were searched using MEDLINE, PubMed, SCOPUS and Web of Knowledge. Unpublished literature, trials in progress, and recent reviews were also searched. Original articles were selected by two investigators. To be included, the study must have compared serum IGFBP-1 in two populations: either PCOS versus controls, or an overweight subgroup versus the normal weight subgroup in either population. From 617 identified articles, 12 were included in the meta-analysis. Data were abstracted by two reviewers independently and standardized for errors. RESULTS: The population difference is presented as the Weighted Mean Difference (95% CI). PCOS subjects had a significantly lower serum concentrations of IGFBP-1 compared with controls [P< 0.00001; -36.6 (-52.0, -21.2) µg/l]. Overweight PCOS subjects also had lower IGFBP-1 levels compared with normal weight PCOS subjects [P < 0.006; -30.6 (-52.3, -8.8) µg/l]. No significant difference was found between overweight PCOS patients and overweight controls [P = 0.23; -5.1 (-13.5, 3.2) µg/l] or between normal weight PCOS patients and normal weight controls [P = 0.50; -3.8 (-14.9, 7.3) µg/l]. Overweight controls had significantly lower IGFBP-1 concentrations than normal weight controls [P = 0.03; -18.0 (-34.4, - 1.5) µg/l]. CONCLUSION: These data indicate that a decreased serum level of IGFBP-1 is unlikely to be a mechanism for ovarian hyperandrogenism in PCOS. BMI may be the major determinant of serum IGFBP-1.

COPD prevalence and its association with occupational exposures in a general population.

The aim of this study was to ascertain the population prevalence of chronic obstructive pulmonary disease (COPD) in an area with past heavy industry and to establish the relative contributions of occupational and other risk factors. We investigated respiratory symptoms and the prevalence of spirometrically-defined COPD in a population-based study in North-East England (UK) between 2002 and 2004. Questionnaires were posted to 6,000 males and 6,000 females, 45-69 yrs of age, who were randomly selected from a primary care database (response rate 64%, n = 7,566). Spirometric measurements were performed on 845 randomly selected responders. We defined COPD by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II criteria. The prevalence of respiratory symptoms was 55%. Symptoms were strongly associated with smoking, occupational exposures and hay fever. COPD was present in 10% of subjects. Its presence was significantly associated with occupational exposures, smoking and hay fever. COPD is common in North-East England. Respiratory effects of occupational exposures can be detected within the general population: there were clear associations between occupational exposures and respiratory symptoms. The association with COPD was more marked in females.

Occupational and environmental lung disease: occupational asthma.

Occupational exposures cause 10-15% of new-onset asthma in adults, and that represents a considerable health and economic burden. Exposure to many causative agents is now well controlled but workplace practices are constantly evolving and new hazards being introduced. Overall, there is no good evidence that the incidence of occupational asthma is decreasing. Evidence-based guidelines such as those published by the British Occupational Health research Foundation and Standards of Care documents should help raise awareness of the problem and improve management. Key targets include the control of occupational exposures, a high index of suspicion in any adult with new onset asthma, and early detailed investigation.

Apparent but not real increase in asthma prevalence during the 1990s.

The authors investigated changes in asthma prevalence and perception of bronchoconstriction over 6 yrs in adults of Newcastle-upon-Tyne. Postal questionnaires were sent to 6,000 subjects aged 20-44 yrs in 1992-1993 and 1998-1999. Random samples of 600 responders had assessments of atopy, airway responsiveness, and their ability to perceive methacholine-induced bronchoconstriction. The prevalences of asthmatic symptoms, physician-diagnosis, and medication use increased by an average of 4.4%, particularly in subjects aged <30 yrs (8.7 versus 2.7). Atopy prevalence increased from 25% to 31% but atopics and nonatopics had similar mean changes in questionnaire data (5.2 versus 3.4). The probability of a positive methacholine test decreased as did the mean methacholine dose/response slope (0.00527 to 0.00379), indicating lower levels of airway responsiveness. This can be largely explained by an increase in use of inhaled corticosteroids (5.0-9.3%). The proportion of subjects perceiving bronchoconstriction during methacholine tests increased from 63 to 77%. The authors conclude that current changes in asthma epidemiology in adults may result from increased awareness of symptoms (and/or an increased willingness to report them), and from an increased willingness of physicians to make the diagnosis and prescribe treatment, not from increased disease prevalence.

Asthmagenicity of coal mine roof-bolting resins: an assessment using inhalation provocation tests.

Inhalation provocation tests were used to assess whether the volatile products of an activated resin had caused occupational asthma in a non-random sample of six asthmatic coal miners. The resin system uses the polymerization of polyester and styrene under the influence of the cross-linking agent dibenzoyl peroxide to secure roof, wall and floor bolts in mine tunnels. The tests were conducted sequentially in a double-blind fashion over a 'dose' range which extended just beyond the maximum likely to have been experienced occupationally during a single day's work. The tests were monitored by symptoms, changes in the forced expiratory volume in 1 s (FEV1) and changes in airway responsiveness. All subjects completed the series of tests without any significant decrements in FEV1 or significant increases in airway responsiveness. We conclude that the use of this resin system is not likely to have been the cause of the asthma in the test subjects, nor in the larger group of miners of which they were a sample, but neither possibility is fully excluded and the participants may not have been adequately representative of other asthmatic coal miners.

Determinants of whether occupational agents cause early, late, or dual asthmatic responses.

Early asthmatic responses to aeroallergens can be predicted from skin prick tests and the level of airway responsiveness. High-molecular-weight occupational agents ought to behave in the same way, but this has not been established sufficiently to allow challenge tests to be avoided. Responses to low-molecular-weight agents are difficult to predict because of the absence of a good measure of sensitization. Late responses appear more common with these agents, but this may be in part a consequence of the single-dose challenge protocol that is commonly used. The pattern of response also is likely to be influenced by the length of time from the last exposure, and the use of medication.

Age-dependent inaccuracy of asthma death certification in Northern England, 1991-1992.

Asthma mortality appeared to increase two-fold in the UK from the mid- 1970s to the early 1990s, but there is evidence of inaccuracy in asthma death certification and so a region-wide investigation was undertaken to assess whether this recorded statistical trend might have been partly or wholly artefactual. A total of 35 respiratory physicians, distributed in panels of three, systemically reviewed the hospital and general practice records of 210 subjects with physician-diagnosed asthma who died in 1991 and 1992. The death certificates indicated that asthma was considered to be the primary cause of death in 103 (group 1), a contributory cause in 70 (group 2) and not relevant in 37 (group 3). There was agreement within the panels that 43% of the subjects had probably never suffered from asthma. Discordance between the panels and the certifying physicians over the correct death certification category was high for group 1 (45% for those aged <65 yrs, 75% for those aged > or =65 yrs and 64% overall) and group 2 (67%), but much less for group 3 (22%). This study concludes that asthma death certification provides a markedly inaccurate picture of asthma mortality, particularly in elderly subjects. Thus, it is speculated that if the magnitude of this source of inaccuracy has increased over the last two decades, the apparent recent increase in asthma mortality may be largely artefactual.

Perception of respiratory symptoms after methacholine-induced bronchoconstriction in a general population.

In an epidemiological study, methacholine-induced bronchoconstriction was used as a physical illustration of the sensations associated with asthma. The objective of this study was to assess whether familiarity with these sensations could be used as a measure of asthma prevalence. Eight hundred and seventy six subjects aged 20-44 yrs completed a respiratory questionnaire and a measurement of airway responsiveness (the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20)). Subjects were asked about their perception of, familiarity with and description of the respiratory sensations experienced at the time of maximal bronchoconstriction. The questionnaire-derived lifetime prevalences of wheeze, chest tightness and undue breathlessness were 43, 35 and 22% respectively. Asthma medication was used by 8% and the lifetime prevalence of diagnosed asthma was 12%. Quantifiable levels of airway responsiveness were measured in 34%, and airway responsiveness in the range considered to be consistent with untreated active asthma was present in 21%. Bronchoconstriction was perceived by 59%. Perception of bronchoconstriction was associated with the magnitude of bronchoconstriction, younger age, female sex and questionnaire-reported symptoms. Of subjects able to perceive bronchoconstriction, 58% reported previous experience of (familiarity with) the associated respiratory sensations. Familiarity with the sensations of bronchoconstriction was associated with questionnaire-reported symptoms, diagnosed asthma and increasing levels of airway responsiveness. There was poor agreement between the respiratory symptoms reported by questionnaire before the methacholine test and the words used to describe respiratory sensations induced by the test. Familiarity with the sensations of methacholine-induced bronchoconstriction has all the appropriate associations of a measure of asthma prevalence and may be a useful adjunct to symptom questionnaires and airway responsiveness measurements in epidemiological studies. A sizeable number of subjects can be identified with intermediate levels of airway responsiveness, who are able to perceive bronchoconstriction and are familiar with the sensations associated with it, yet who are not recognized to suffer from asthma.

Occupational asthma in an isothiazolinone manufacturing plant.

A chemical plant operator developed asthma five months after starting work in an isothiazolinone manufacturing plant. He described symptoms of late asthmatic reactions after work with isothiazolinone. Airway responsiveness to methacholine improved tenfold when he was removed from the plant for 18 days. A workplace challenge study then resulted in a deterioration in airway responsiveness to its earlier level and in progressive falls in forced expiratory volume in one second (FEV1) over three days at work compared with control days, indicating statistically significant late asthmatic reactions of increasing severity.

An epidemiologic investigation of asthma in welders.

To clarify whether asthma may be caused by fume from welding mild steel and to evaluate the possible strength of such an effect, we quantified airway responsiveness among young shipyard workers with different levels of fume exposure. Clinical investigation comprised a cross-sectional survey of 19- to 27-yr-old workers who were completing 3 to 9 yr of employment in various trades, and a control group of 15- to 17-yr-old school leavers who were applying for apprenticeships within the same trades. Both groups were subdivided into negligible-, ambient-, or high-exposure subgroups according to expected levels of fume exposure. Actual exposures were assessed in a parallel environmental survey. Participants were investigated by questionnaire, skin prick tests, spirometry, and methacholine tests. Complete data sets were obtained from 1,024 of the 1,070 eligible subjects (96%). Among the workers but not the school leaver controls, there was an increasing prevalence of positive methacholine tests across the exposure subgroups-negligible 37%, ambient 44%, high 49% (p < 0.05). Regression analyses showed that in males after allowing for the effects of atopy, current smoking, and age, the estimated geometric mean level of airway responsiveness of regular welders was twice that of workers with negligible exposure after 5 yr of work. This implies that fume exposure may have been critical in causing asthma in about 1% of the welders. A lesser effect (though not significantly so) was noted among the workers with ambient exposure.

Occupational tuberculosis and a failed postgraduate medical examination.

A 40 year old pathologist presented with a tuberculous pleural effusion approximately one year after performing an autopsy as part of a postgraduate medical examination. She had made a diagnosis of disseminated tuberculosis but was told that this was incorrect and failed the examination. Bladder tissue from the cadaver was subsequently found to have grown M tuberculosis though none was cultured from lung tissue. No particular precautions against airborne infection were taken at the time of the autopsy and we speculate not only that the pathologist's original diagnosis was correct but that she became infected with M tuberculosis during the examination.

Asthma, airways responsiveness and air pollution in two contrasting districts of northern England.

BACKGROUND: To assess the possible magnitude of differences between normal populations an epidemiological investigation of asthma was conducted in two strongly contrasting districts of northern England--rural West Cumbria on the west coast and urban Newcastle upon Tyne on the east coast. METHODS: A cross sectional survey of randomly identified men aged 20-44 years was conducted in two phases: phase 1, a postal survey of respiratory symptoms and asthma medication in 3000 men from each district; and phase 2, a clinical assessment of 300 men from each district comprising investigator administered questionnaires, skin prick tests, spirometry, and methacholine challenge tests. RESULTS: The phase 1 (but not phase 2) study showed a small excess of "ever wheezed" in Newcastle (44% versus 40%), but neither phase showed differences between the two districts for recent wheeze or for other symptoms characteristic of asthma. There were also no differences with regard to diagnosed asthma, current asthma medication, spirometric parameters, or airways responsiveness. The prevalence of quantifiable airways responsiveness (PD20 < or = 6400 micrograms) was 27.7% in West Cumbria and 28.2% in Newcastle. Regression analyses showed that PD20 was negatively associated with atopy and positively with forced expiratory volume in one second (FEV1); that an association between PD20 and current smoking could be explained by diminished FEV1; and that PD20 was not related to geographical site of residence. CONCLUSIONS: Neither airways responsiveness nor the other parameters of diagnostic relevance to asthma varied much between the two study populations, despite the apparent environmental differences. The most obvious of these were the levels of outdoor air pollution attributable to vehicle exhaust emissions, the ambient levels of which were 2-10 fold greater in Newcastle. Our findings consequently shed some doubt over the role of such pollution in perceived recent increases in asthma prevalence. It is possible, however, that an air pollution effect in Newcastle has been balanced by asthmagenic effects of other agents in West Cumbria.