Recombinant ADAMTS13 normalizes von Willebrand factor‐cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies

Summary. Background: Severe deficiency of the von Willebrand factor (VWF)‐cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non‐inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently replenish the deficient enzyme. Objectives: To explore the use of recombinant ADAMTS13 (rADAMTS13) as a potential therapeutic agent in acquired TTP, we investigated its efficacy in normalizing VWF‐cleaving activity in the presence of ADAMTS13 inhibitors. Methods: Thirty‐six plasma samples from TTP patients were adjusted to predefined inhibitor titers, and recovery of ADAMTS13 activity was analyzed following supplementation with rADAMTS13. Results: We showed a linear relation between the inhibitor titer measured and effective rADAMTS13 concentration necessary for reconstitution of VWF‐cleaving activity in the presence of neutralizing autoantibodies. Conclusions: Our results support the further investigation of the potential therapeutic applicability of rADAMTS13 as an adjunctive therapy in acquired TTP.     

Prevalence trends of rhinoconjunctivitis, eczema, and atopic asthma in Greek schoolchildren: four surveys during 1991-2008

After a continuous increase of asthma, hay fever, and eczema during 1991-2003 among schoolchildren in Patras, Greece, the prevalence of current wheeze/asthma (diagnosed wheezing and/or asthma in the past 2 years) has reached a plateau (6.9%) during the period 2004-2008. Using methodology identical to the three previously conducted cross-sectional, parental questionnaire surveys (1991, n = 2417; 1998, n = 3076; 2003, n = 2725) we examined further trends in the prevalence of rhinoconjunctivitis and eczema in the same urban environment among third and fourth grade schoolchildren (8-9 years old) in 2008 (n = 2688). In the four surveys, respective prevalence rates of rhinoconjunctivitis were 2.1, 3.4, 4.6, and 5.1% (absolute prevalence increase: 1998 versus 1991, 61.9%; 2003 versus 1998, 35.5%; 2008 versus 2003, 10.9%) and those of eczema were 4.5, 6.3, 9.5, and 10.8% (absolute prevalence increase: 1998 versus 1991, 40.0%; 2003 versus 1998, 50.8%; 2008 versus 2003, 13.7%; sex-adjusted p for trend, <0.001). Among current wheezer/asthmatic patients there was an increase in lifetime rhinoconjunctivitis (sex-adjusted p for trend, <0.001) and lifetime eczema (sex-adjusted p for tend, <0.001) over the period 1991-2008. The proportion of atopic wheeze/asthma (current asthma with lifetime rhinoconjunctivitis and/or eczema) increased further during 2003-2008 (p < 0.05; p for trend during 1991-2008, <0.001). In conclusion, there is a continuous increase in the prevalence of allergic manifestations-rhinoconjunctivitis and eczema-among preadolescent children in Patras, Greece, during the period 1991-2008. After a steep rise during 1991-2003, the frequency of atopic wheeze/asthma continued to increase at a decelerating rate during 2003-2008, while wheeze/asthma prevalence remained unchanged during the same 5-year period.     

Pulse oximetry in pediatric practice

The introduction of pulse oximetry in clinical practice has allowed for simple, noninvasive, and reasonably accurate estimation of arterial oxygen saturation. Pulse oximetry is routinely used in the emergency department, the pediatric ward, and in pediatric intensive and perioperative care. However, clinically relevant principles and inherent limitations of the method are not always well understood by health care professionals caring for children. The calculation of the percentage of arterial oxyhemoglobin is based on the distinct characteristics of light absorption in the red and infrared spectra by oxygenated versus deoxygenated hemoglobin and takes advantage of the variation in light absorption caused by the pulsatility of arterial blood. Computation of oxygen saturation is achieved with the use of calibration algorithms. Safe use of pulse oximetry requires knowledge of its limitations, which include motion artifacts, poor perfusion at the site of measurement, irregular rhythms, ambient light or electromagnetic interference, skin pigmentation, nail polish, calibration assumptions, probe positioning, time lag in detecting hypoxic events, venous pulsation, intravenous dyes, and presence of abnormal hemoglobin molecules. In this review we describe the physiologic principles and limitations of pulse oximetry, discuss normal values, and highlight its importance in common pediatric diseases, in which the principle mechanism of hypoxemia is ventilation/perfusion mismatch (eg, asthma exacerbation, acute bronchiolitis, pneumonia) versus hypoventilation (eg, laryngotracheitis, vocal cord dysfunction, foreign-body aspiration in the larynx or trachea). Additional technologic advancements in pulse oximetry and its incorporation into evidence-based clinical algorithms will improve the efficiency of the method in daily pediatric practice.     

Sex-specific trends in prevalence of childhood asthma over 30 years in Patras, Greece

Aim: According to four surveys conducted during 1978–2003, the prevalence of childhood asthma and wheezing has risen in the city of Patras, Greece, albeit at a decelerating rate. We examined sex‐specific wheeze and asthma prevalence in the same urban environment in 2008. Methods: A cross‐sectional parental questionnaire survey was performed in 2008 among third and fourth grade schoolchildren (8–9 year old), which was identical to previously conducted surveys in 1978 (n = 3003), 1991 (n = 2417), 1998 (n = 3076) and 2003 (n = 2725). Results: The prevalence of current wheeze and asthma in 1978, 1991, 1998, 2003 and 2008 (n = 2688) was 1.5%, 4.6%, 6.0%, 6.9% and 6.9%, respectively (p for trend <0.001). Respective values for lifetime (ever had) wheeze and asthma in the 1991–2008 surveys were 8.0%, 9.6%, 12.4% and 12.6% (p for trend <0.001). The male:female ratio of current and lifetime wheeze and asthma increased during the 30‐year surveillance period (p for trend <0.001). Irrespective of sex, diagnosed asthma declined among current wheezers by 17% (p < 0.001), but not among non‐current ones (6.7%, p = 0.16) during 2003–2008. Conclusions: Childhood wheeze and asthma have reached a plateau in an urban environment in Greece, while the male:female ratio increased. Asthma diagnosis declined among schoolage but not preschool wheezers during 2003–2008.     

A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease

BACKGROUND:

Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV₁) than those patients who have stopped smoking.

OBJECTIVES:

To assess the effect of tiotropium on pre-dose (trough) FEV₁ in patients with COPD followed in Canada.

METHODS:

A total of 913 patients were randomly assigned to receive either tiotropium 18 μg once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV₁, FEV₆ and forced vital capacity), symptoms, health-related quality of life (St George’s Respiratory Questionnaire) and exacerbations were examined.

RESULTS:

Tiotropium improved trough FEV₁ in both current and ex-smokers compared with placebo. Baseline FEV₁ in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14±0.04 L (P<0.001) in the smoker group and 0.08±0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV₆ compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George’s Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005).

CONCLUSIONS:

Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.     

Priorities for future research into asthma diagnostic tools: A PAN‐EU consensus exercise from the European asthma research innovation partnership (EARIP)

The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two‐stage e‐Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two‐stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face‐to‐face workshop. The three most important diagnostic/predictive tools ranked were as follows: “New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring,” “Prediction of future asthma in preschool children with reasonable accuracy” and “Tools to measure volatile organic compounds (VOCs) in exhaled breath.”