New insights into the relationship between airway inflammation and asthma

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.     

Amplitude variation in static-charge-sensitive bed signal increased in obstructive airways disease

The relationship between oesophageal pressure variation and amplitude variation in the static-charge-sensitive bed (SCSB) ballistocardiogram suggests that changes in intrathoracic pressure can be detected using the SCSB method. We investigated whether amplitude variation in the static-charge-sensitive bed ballistocardiogram (SAV) is related to severity of airway obstruction in patients with asthma and chronic obstructive pulmonary disease. The ability of SAV to detect an increase in airway obstruction induced by histamine challenge was also tested. Twenty-six patients suffering from asthma and 12 patients with chronic obstructive pulmonary disease (COPD) were enrolled in the study. SAV, amplitude from the SCSB ballistocardiogram, respiratory amplitude from the SCSB respiratory wave form and heart rate from the electrocardiogram (ECG) were computed using analysing software (Biorec, Helsinki, Finland) during a 7-min supine rest. SAV was related to forced expiratory volume in one second (FEV₁) immediately after signal recording. Asthma patients participated in a standardized histamine challenge test to reveal the effect of acute bronchoconstriction on SAV. An inverse relationship existed between baseline FEV₁ and SAV in asthma and COPD. In the histamine inhalation test, FEV₁ fell by 0·7 ± 0·3 l or 26% ± 11% (P<0·0001) and SAV increased by 12% ± 5% (P<0·0001) in 12 asthma patients. The fall in FEV₁ induced by histamine followed regularly and correlated significantly with the rise in SAV (n = 24, r = ?0·58, P = 0·002). Changes in respiratory amplitude or heart rate did not explain changes in SAV. SAV may not separate the upper airway obstruction from the bronchial obstruction but it is related to severity of airway obstruction. The clinically significant increase in airway obstruction induced by histamine inhalation increases amplitude variation in SCSB.     

Evidence-based implementation of adult asthma guidelines in the emergency department: a controlled trial

Objective: To determine if an evidence‐based implementation (EBI) strategy could lead to the successful implementation of guidelines for the management of adult asthma in a large rural ED. Methods: This was a pre‐ and post‐intervention trial, comparing data for seven clinical indicators from a study hospital and a control hospital. Retrospective pre‐intervention audits were conducted at the study hospital for 3 months (1 April?30 June 2004) and the control hospital for 4 months (1 March?30 June 2004). The effect of an EBI to implement established guidelines for the management of asthma at the study hospital was compared with the effect of a mail‐out of guideline booklets and wall charts to the control hospital. Post‐intervention audits were then performed at both hospitals. Sustainability of the EBI was gauged by 12 month follow‐up data at the study hospital. Results: There were 55 presentations of adult asthma at the study hospital in the pre‐intervention phase and 67 post‐intervention. The corresponding numbers for the control hospital were 51 and 42, respectively. Following the EBI there were significant improvements at the study hospital for the documentation of severity (27–99%, P < 0.01), use of spirometry (38–84%, P < 0.01), medication delivery via spacer device (0–26%, P < 0.01), use of systemic steroids (66–84%P < 0.05), use of written short‐term asthma plans (14–82%, P < 0.01), reduction of ipratropium use in mild asthma (43–16%, P < 0.05) and reduction in antibiotic use in afebrile asthmatics (37–6%, P < 0.01). For the control hospital there was a significant increase in spirometry use from 2% to 40% (P < 0.01). For seven clinical indicators combined, compliance with the guideline increased from 38% to 79.1% (P < 0.01) at the study hospital, whereas there was no change at the control hospital, 44.3% to 43% (P = 0.75) There were 68 presentations at 12 month follow up at the study hospital and compliance with the seven clinical indicators was 78.2%. Conclusion: An EBI significantly improved compliance at the study hospital with no improvement noted in the control hospital. These improvements were maintained at 12 month follow up. An EBI can lead to significant improvements in the management of asthma at a large rural referral hospital ED and might have implications for hospitals with similar roles and profiles.     

Evaluation of a falls prevention programme in an acute tertiary care hospital

Aims and objectives. To evaluate a systematic, coordinated approach to limit the severity and minimize the number of falls in an acute care hospital. Background. Patient falls are a significant cause of preventable injury and death, particularly in older patients. Best practice principles mandate that hospitals identify those patients at risk of falling and implement interventions to prevent or minimize them. Methods. A before and after design was used for the study. All patients admitted to three medical wards and a geriatric evaluation management unit were enrolled over a six‐month period. Patients’ risk of falling was assessed using a falls risk assessment tool and appropriate interventions implemented using a falls care plan. Data related to the number and severity of falls were obtained from the Australian Incident Monitoring System database used at the study site. Results. In this study, 1357 patient admissions were included. According to their risk category, 37% of patients (n = 496) were grouped as low risk (score = 1–10), 58% (n = 774) medium risk (score = 11–20) and 5% (n = 63) high risk (score = 21–33) for falls. The incidence of falls (per average occupied bed day) was eight per 1000 bed days for the study period. Compared with the same months in 2002/2003, there was a significant reduction in falls from 0·95 to 0·80 (95% CI for the difference ?0·14 to ?0·16, P < 0·001). Conclusion. We evaluated a systematic, coordinated approach to falls management that included a falls risk assessment tool and falls care plan in the acute care setting. Although a significant reduction in falls was found in this study, it could not be attributed to any specific interventions. Relevance to clinical practice. Preventing falls where possible is essential. Assessment of risk and use of appropriate interventions can reduce the incidence of falls.     

Bronchial obstruction after oesophageal acid perfusion in asthmatics

Summary. Fifteen patients with the combination of bronchial asthma and symptoms of gastro-oesophageal reflux reproduced at endo-oesophageal acid perfusion (group I) were investigated to detect bronchial obstruction, reflexly elicited from the distal oesophagus. Five patients with bronchial asthma but without symptoms of gastro-oesophageal reflux (group 2) and five patients with symptoms of gastro-oesophageal reflux but without respiratory symptoms (group 3) served as controls. The vital capacity (VC), the slope of the alveolar plateau (δN₂) and the closing volume (CV) were measured with the single breath nitrogen test before and after acid perfusion of the oesophagus, and again after antacid and glucose perfusion of the oesophagus. In group 1 a significant decrease of VC by 0–21 (P<0–001) and a significant increase of δN₂ by 0–9% (P<005) was seen while no change in CV was found. There was no change after acid perfusion in groups 2 or 3. After glucose and antacid the VC increased significantly in group 1 while no significant change was seen in δN₂ or CV. These findings were taken as indirect evidence of bronchial obstruction induced by the acid infusion. Since the changes were provoked in the sitting position and only in asthmatics with a positive acid perfusion test and since no patient complained of acid taste in the mouth it is unlikely that the bronchial obstruction was due to aspiration. A neural oesophago-bronchial reflex mechanism is suggested.     

Reflex inhibition of the quadriceps after meniscectomy: lack of association with pain

Summary. We have examined the severity and duration of reflex inhibition of quadriceps activation after arthrotomy and meniscectomy, its relationship with pain, and the effect of local anaesthesia on this relationship. Fourteen men, on completion of medial meniscectomy by arthrotomy, received either 10 ml (BIO group) or 15 ml (B15 group) of 0–5% bupivacaine hydrochloride (‘Marcaine Plain’) into the knee, or no injection (control group). Reflex inhibition of quadriceps was measured as the percentage reduction, from the ipsilateral preoperative value, in the integrated surface electromyogram recorded during maximal voluntary isometric contractions with the knee in extension. Pain during each contraction was recorded on a linear analogue scale. Unoperated limbs showed no evidence of quadriceps inhibition. In the operated limbs, at 1–2 h post-operatively, controls had both severe inhibition (median = 62%) and severe pain on attempting a maximal quadriceps contraction. The BIO group had similar inhibition but less pain (P= s 0–005, Wilcoxon 2-sample, 1-tailed test). In the B15 group both inhibition (P 0–05) and pain (P 0–01) were less than in the controls. These effects of bupivacaine had been lost by 4–5 h post-operatively. At 3–4 days, inhibition was still severe (median=75%) in all three groups of patients but pain was only mild or absent. At 10–15 days, median inhibition was still 35%, but there was little or no pain. We conclude that postmeniscectomy inhibition is not simply due to perceived pain but is due, at least in part, to stimuli from the knee.     

Evidence-based hypnotherapy for asthma: a critical review

Asthma is a chronic disease with intermittent acute exacerbations, characterized by obstructed airways, hyper-responsiveness, and sometimes by chronic airway inflammation. Critically reviewing evidence primarily from controlled outcome studies on hypnosis for asthma shows that hypnosis is possibly efficacious for treatment of symptom severity and illness-related behaviors and is efficacious for managing emotional states that exacerbate airway obstruction. Hypnosis is also possibly efficacious for decreasing airway obstruction and stabilizing airway hyper-responsiveness in some individuals, but there is insufficient evidence that hypnosis affects asthma's inflammatory process. Promising research needs to be replicated with larger samples and better designs with careful attention paid to the types of hypnotic suggestions given. The critical issue is not so much whether it is used but how it is used. Future outcome research must address the relative contribution of expectancies, hypnotizability, hypnotic induction, and specific suggestions.     

Effectiveness of budesonide administered via dry-powder inhaler versus triamcinolone acetonide administered via pressurized metered-dose inhaler for adults with persistent asthma in managed care settings

BACKGROUND: Clinical studies have demonstrated the efficacy and relative safety of inhaled corticosteroids in the treatment of asthma. However, effectiveness and cost-effectiveness comparisons of available inhaled corticosteroids in real-life clinical settings are lacking. OBJECTIVE: This study compared the effectiveness and safety of budesonide administered via dry-powder inhaler versus that of triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adult patients with persistent asthma treated in a managed care setting. METHODS: This was a randomized, open-labe, 52-week study of adult patients (aged >or= 18 years) with persistent asthma enrolled in 25 US health plans. The primary study outcome was mean change from baseline to the end of treatment in symptom-free days. Secondary variables were changes from baseline in number of episode-free days, episode-free days at 52 weeks, forced expiratory volume in 1 second (FEV(1)), forced vital capacity, asthma symptom scores, breakthrough bronchdilator use, patient discontinuations, and health-related quality of life. Patients were issued diaries in which to record use of study medication and concomitant asthma medication use, as well as daytime and nighttime asthma symptom severity. Patients were assessed at weeks 4, 13, 26, 39, and 52. Safety was assessed based on adverse events and changes in laboratory tests, vital signs, and physical examinations. RESULTS: A total of 945 patients (344 men, 601 women; mean [SD] age, 46.8 [14] years) were enrolled; 631 received budesonide and 314 received triacinolane acetonide. Improvements in all effectiveness variables were observed with both treatments. The mean increase from baseline in the number of symptom-free days per month assessed at month 12 was 7.74 (95% CI, 6.81-8.66) for patients receiving budesonide and 3.78 (95% CI, 2.47-5.09) for patients receiving triamcinoline acetonide ( P<0.001). The estimated annual mean (SD) number symptom-free days for patients receiving budesonide was 141.1 (125.0) over the treatment phase, compared with 99.3 (112.1) for those receiving triamcinolone acetonide (P<0.001). Patients receiving budesonide demonstrated significant improvements (compared with those receiving triamcinolone acetonide) in overall quality of life, daytime and nighttime asthma symptom severity, breakthrough bronchodilator use, and FEV(1) (all P<0.001). Safety measures were similar between groups. CONCLUSION: In these managed care settings, budesonide inhalation powder administered via dry-powder inhaler was significantly more effective than triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adults with persistent asthma.     

Prospective Evaluation of Two Clinical Scores for Acute Asthma in Children 18 Months to 7 Years of Age

Objectives: The objective was to evaluate the discriminatory ability of two clinical asthma scores, the Preschool Respiratory Assessment Measure (PRAM) and the Pediatric Asthma Severity Score (PASS), during an asthma exacerbation. Methods: This was a prospective cohort study in an academic pediatric emergency department (ED; 60,000 visits/year) conducted from March 2006 to October 2007. All patients 18 months to 7 years of age who presented for an asthma exacerbation were eligible. The primary outcome was a length of stay (LOS) of >6 hours in the ED or admission to the hospital. Clinical findings and components of the PRAM and the PASS were assessed by a respiratory therapist (RT) at the start of the ED visit and after 90 minutes of treatment. Results: During the study period, 3,845 patients were seen in the ED for an asthma exacerbation. Of these, 291 were approached to participate, and eight refused. Moderate levels of discrimination were found between a LOS of >6 hours and/or admission and PRAM (area under the receiver‐operating characteristic curve [AUC] = 0.69, 95% confidence interval [CI] = 0.59 to 0.79) and PASS (AUC = 0.70, 95% CI = 0.60 to 0.80) as calculated at the start of the ED visit. Significant similar correlations were seen between the physician’s judgment of severity and PRAM (r = 0.54, 95% CI = 0.42 to 0.65) and PASS (r = 0.55, 95% CI = 0.43 to 0.65). Conclusions: The PRAM and PASS clinical asthma scores appear to be measures of asthma severity in children with discriminative properties. ACADEMIC EMERGENCY MEDICINE 2010; 17:598–603 © 2010 by the Society for Academic Emergency Medicine     

The Prevalence,Characteristics, and Patient Burden of Severe Asthma Determined by Using a Japan Health Care Claims Database

BackgroundRecently, several new biological drugs targeting severe asthma are on the market, and various studies on severe asthma have been reported worldwide. However, in Japan, the data are still limited regarding epidemiology and burden of disease on severe asthma. This study determined the prevalence, characteristics, and burden of disease of patients with severe asthma.Methods: This retrospective study (HO-16-16484) used a nationwide health care claims database. Severity of asthma was defined according to the treatment during the baseline period (April 1, 2014–March 31, 2015). Eligible patients were >15–65 years of age with asthma during the 12-month baseline period and were followed up for 12 months. End points included the prevalence, characteristics, exacerbation frequency, and patient behavior in patients with severe, moderate, or mild asthma. Risk factors for exacerbations were explored in patients with all levels of asthma severity and in those with severe asthma.FindingsAmong the 16,107 patients with asthma, 2.4 (95% CI, 2.1–2.6) per 100 patients had severe asthma. During the baseline period, 130 (34.0%) of 382 patients with severe asthma had ≥1 asthma exacerbation. The exacerbation frequency was highest in patients with severe asthma, and most of the comorbidities increased in proportion to the asthma severity. During the follow-up period, exacerbation frequency increased with asthma severity. Approximately 70% of patients with severe asthma were treated at clinics, requiring outpatient visits ~10 times per year. Different exacerbation risk factors were identified between patients with all severity levels of asthma and those with severe asthma. With the severe asthma patients, experiencing exacerbations during the previous year was a risk factor for further exacerbations during the follow-up period.ImplicationsIn Japan, 2.4% of patients with asthma have severe asthma, and there is a significant burden of disease in patients with severe asthma undergoing high-intensity treatment.     

Peak flow values by gestation in women with asthma

Asthma is one of the most common medical complications of pregnancy. Asthma control is associated with improved perinatal outcomes. Peak flow measures have been recommended to determine the status of asthma, yet norms for peak flow values in women with asthma are missing from the literature. The purpose of this study was to determine average peak flow values in pregnant women with asthma. Forty-three women were recruited into the study prior to the 20th week of pregnancy. Demographic data, including age, ethnic background, and number of pregnancies, were collected. Type and severity of asthma, medications used for asthma, and past hospitalizations for asthma were recorded. Peak flow values increased across the three trimesters. Significant differences were found in peak flow values between the first and third trimesters (>.001) and the second and third trimesters (>.007). Findings from the present study contradict those of studies on pregnant women without asthma.     

A retrospective study of the patients with positive ImmunoCard Mycoplasma test on an outpatient clinic basis

The simplified ImmunoCard Mycoplasma test for rapidly detecting Mycoplasma pneumoniae-specific IgM antibodies has been widely used. We examined the usefulness of this test for outpatient practices as well as for the association with bronchial asthma. Among 196 patients whose ImmunoCard showed positive, we targeted 57 cases in which we were able to perform this test multiple times. We evaluated the degree of inflammatory response in the laboratory findings at the time of the test, the period until negative seroconversion for antibodies, and the course of their pulmonary function findings. The number of days from the onset of pyrexia until the test was a median of 10 (range 2–70) days, wherein the inflammatory response did not have a significant effect on that number of days. In 35 cases in which we observed the seroconversion to negative for antibodies, the period of the positive phase was 180 (21–421) days, wherein it was significantly longer for smokers. We observed exacerbation in the majority of the asthma patients, and some of the non-asthmatic patients showed either asthma or asthma-like clinical conditions. For ImmunoCard-positive individuals, it is desirable to ascertain the history of respiratory infection retrospectively to about half a year, although this test is known to suffer from lack of both of sensitivity and specificity. Additionally, it is necessary for ImmunoCard-positive patients to pay attention to the exacerbation of asthma and the development of asthma thereafter.     

气道反应性增高的危险因素分析

目的:分析气道高反应性的危险因素.方法:对怀疑支气管哮喘的患者行支气管激发试验,按检查结果分为研究组(气道反应增高,n=88)和对照组(气道反应正常,n=114),比较两组的临床指标;同时应用logistic回归分析筛选气道高反应的危险因素.结果:研究组和对照组的喘息症状发生率(10.2％ vs 0.9％)、病程＞1年(34.1％ vs 7.0％)、吸烟率(44.3％ vs 29.8％)、过敏性鼻炎发生率(31.8％ vs 13.2％)、哮喘家族史(52.3％ vs7.0％)及小气道功能异常发生率(40.9％ vs 20.2％)均有显著差异;年龄＜40岁(OR值2.800),病程＞1年(OR值13.051)、喘息症状(OR值32.743)、过敏性鼻炎病史(OR值3.380)、哮喘家族史(OR值26.811)和小气道功能异常(OR值4.228)是气道高反应的危险因素.结论:应用一些简单、易测的临床指标能协助预测气道反应性增高,其中喘息症状、病程＞1年和哮喘家族史具有较高的预测价值.     

Compliance of adolescents with asthma

The purpose of this paper is to describe the health regimen compliance of adolescents with asthma and some factors related to it. The following research questions were addressed: (i) to what extent do adolescents with asthma comply with health regimens; and (ii) what type of factors are associated with compliance of adolescents with asthma? A total of 300 individuals aged 13–17 years were randomly selected from the Finnish Social Insurance Institution’s register. Every 15th person on the list was included in the sample and were sent questionnaires. A total of 88% (n = 266) of adolescents returned the questionnaire. The results showed that 42% of the adolescents with asthma complied fully with the health regimens, 42% placed themselves in the category of satisfactory compliance, and the remaining 18% reported poor compliance. Compliance with the need to avoid foods, animals and pollens that cause asthma attacks was poorest, while the highest degree of compliance was observed for medication and control visits to medical staff. Background variables, such as age, family size, exercise, smoking, alcohol intake and severity of disease, were significantly associated with compliance (P < 0.001). Good motivation, a strong sense of normality, energy and will-power, support from the parents, physicians and nurses, a positive attitude towards the disease and treatment, no threat to social wellbeing and no fears of complications had statistically significant relation to good compliance (P < 0.001).     

Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator

Background Acute axonal polyneuropathy has been found in patients with multiple organ dysfunction syndrome. This critical illness polyneuropathy (CIP) has been associated with difficult weaning from the ventilator in retrospective studies.Objective To test the hypothesis that CIP is related to the degree and number of organ dysfunctions, and to weaning problems.Design Prospective study of 18 months.Setting A multidisciplinary intensive care unit in a general hospital.Subjects Thirty-eight patients under 75 years of age who had been mechanically ventialted for more than 7 days, without previous signs of or risk factors for polyneuropathy.Measures Organ dysfunctions were quantified using a dynamic scoring system (0–12 points). Electromyography studies were performed during mechanical ventilation to identify patients with and without CIP.Results CIP was present in 18 out of 38 patients and associated with an increased organ dysfunction score (5.3±1.8 vs. 3.6±1.5;p=0.003) and number of organs involved [median (range): 4 (3–5) vs. 2 (1–4);p=0.009], in particular cardiovascular (p=0.003), renal (p=0.04), and hematopoietic failure (p=0.04). Patients with polyneuropathy were ventilated longer, but this was not clearly due to more difficult weaning [median: 16.5 (1–48) vs. 9.5 (1–38) days;p=0.26]. Polyneuropathy was present in 2 of 4 patients with normal weaning.Conclusions Axonal polyneuropathy is related to the severity of multiple-organ-dysfunction syndrome. Its presence does not necessarily implicate difficult weaning from artificial ventilation.Deceased     

Plasma protein thiols: an early marker of oxidative stress in asthma and chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress (OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers (TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma (n = 24) and mild stable COPD (n = 29) and in age‐ and sex‐matched controls. Forced expiratory volume in 1 s (FEV₁) was associated with age both in patients and control groups. By contrast, FEV₁ was positively correlated with PSH only in COPD (ρ = 0·49, P = 0·007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma (OR = 0·32, 95% CI 0·13–0·78, P = 0·01) and COPD (OR = 0·50, 95% CI 0·26–0·95, P = 0·03). These findings suggest that proteins ‐SH are a sensitive OS marker in early COPD and asthma.     

Nitrite in exhaled breath condensate as a marker of nitrossative stress in the airways of patients with asthma,COPD, and idiopathic pulmonary fibrosis

Background: Nitrite and nitrate are exhaled in droplets of an aerosol during breathing and can be assayed in the exhaled breath condensate (EBC) as markers of nitrossative stress in the airways of patients with asthma, COPD, and idiopathic pulmonary fibrosis (IPF). Subjects and methods: Using HPLC with fluorescence detection, nitrite and nitrate were assayed in EBC of 14 atopic patients with mild‐to‐moderate stable asthma, 18 atopic asthmatics with exacerbation, 14 COPD patients without exacerbation, 18 patients with exacerbated COPD, 13 patients with active IPF, and in 29 healthy subjects. Results: The geometric mean [exp(mean±SD)] EBC concentrations of nitrite (micromol/l) in patients with asthma [5.1(2.1–12.3)], exacerbation of asthma [5.1(2.8–9.6)], exacerbation of COPD [5.3(3.2–8.7)], and with IPF [5.5(2.9–10.2)] were higher (P<0.05) compared with those of healthy subjects [2.9(1.6–5.3)] and patients with stable COPD [3.0(1.3–6.7)]. Nitrite concentration increased with decreased lung function of patients with asthma (r_s=?0.31, P<0.02). Presumably owing to the contamination of the EBC sample with nitrate during collection, nitrate levels were highly variable among healthy subjects and higher compared with all groups of patients. Conclusion: EBC nitrite is a suitable marker of nitrossative stress in adult patients with lung diseases but cannot differentiate controlled and exacerbated asthma. Further improvements to the methods of EBC collection and sample handling are warranted. J. Clin. Lab. Anal. 24:317–322, 2010. © 2010 Wiley‐Liss, Inc.     

Measuring disability with parsimony: evidence for the utility of a single item

Purpose: To provide evidence for the utility of a single item measure designed to quantify disability in the past 30 days.

Method: Australian data from studies comprising a community-dwelling elderly sample (N?=?328) and a sample of chronic osteoarthritis (OA) patients (N?=?119) are reported. Degree of disability was classified as 0?–?30 days, 0 vs. 1 or more days, and 0?–?9 vs. 10 or more days. Associations between disability and a range of demographic, health-related, and psychological variables were assessed.

Results: Participants with OA reported a significantly higher level of disability than participants from the community sample regardless of how disability was classified. Modest levels of association were noted between the number of disability days (0?–?30) and both health and psychological indices in both samples. The three alternative classifications of disability made little difference to the significance of associations. On balance, the comparison of 0?–?9 vs. 10 or more days appeared the more predictive classification of disability.

Conclusions: The performance of the single item measure of disability was generally very satisfactory. Future investigations into the clinical application of the item across a range of patient groups are encouraged.     

Pregnancy-associated plasma protein-A and asthma

Pregnancy-associated plasma protein-A (PAPP-A) is potentially a proatherosclerotic metalloproteinase and a new inflammatory marker. Investigators sought to evaluate the significance of PAPP-A in patients with asthma. Blood samples were collected from 35 patients and 20 control subjects. Serum PAPP-A was determined by enzyme-linked immunosorbent assay. PAPP-A levels of patients with asthma (8.1±5.0 mU/L) were higher than those of the control group (4.9±2.1 mU/L) (P < .01). A significant correlation was noted between serum PAPP-A concentration and asthma severity (r=.581;P < .01). Investigators concluded that PAPP-A may contribute to airway smooth muscle hyperplasia as an insulin-like growth factor-dependent insulin-like growth factor-binding protein-4 protease in patients with asthma.     

Efficacy and safety of secondary prophylactic vs. on-demand sucrose-formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13-month crossover study

Summary. Background: Hemarthroses in severe hemophilia precipitate physical, psychosocial and financial difficulties. Objective: To compare the effects of secondary prophylaxis with on‐demand sucrose‐formulated recombinant factor VIII (rFVIII‐FS) therapy in severe hemophilia A. Patients and methods: This open‐label study included patients aged 30–45 years with factor VIII (FVIII) coagulant activity < 1 IU dL^?1 who were using on‐demand FVIII treatment. Patients were treated with rFVIII‐FS on demand for 6 months, followed by 7 months prophylaxis (20–40 IU kg^?1, three times per week, with the first month considered a run‐in). The primary endpoint was the number of hemarthroses. Results: Twenty patients were enrolled (n = 19 completed); the mean age was 36.4 years, and 16 had target joints. The median (25–75%) number of joint bleeds decreased significantly with prophylaxis [0 (0–3)] vs. on‐demand [15 (11–26); P < 0.001] therapy. The number of all bleeds was 0 (0–3) vs. 20.5 (14–37; P < 0.001), respectively. Median (range) total Gilbert scores improved after prophylaxis [18 (3–39)] compared with on‐demand [25 (4–46)] therapy, predominantly reflecting the improved bleeding score. Median time from last prophylactic infusion to bleed was 2 days; 82.5% of bleeds occurred 2–3 days after the last infusion. Median 48‐h and 72‐h FVIII trough levels measured during months 10 and 13 were consistently > 6 and > 4 IU dL^?1, respectively. Treatment was well tolerated, and no inhibitor formation was observed. Conclusion: Secondary prophylaxis with rFVIII‐FS significantly reduced the frequency of hemarthroses compared with on‐demand therapy in adult patients with severe hemophilia A.