Anti-IL-5/5Ra biologics improve work productivity and activity in severe asthma: a RAPSODI registry-based cohort study.

INTRODUCTION: Severe asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment. AIMS AND OBJECTIVES: This study aims to relate treatment with biologics targeting IL-5/5Ra to work productivity and activity in the long term in a real-world context. MATERIAL AND METHODS: This is a registry-based multi-center cohort study evaluating data from adults with severe eosinophilic asthma included in the Dutch Register of Adult Patients with Severe Asthma for Optimal DIsease management (RAPSODI). Patients that started with anti-IL-5/5Ra biologics and completed the work productivity and activity improvement questionnaire, were included. Study and patient characteristics were compared between the employed and unemployed patients. Work productivity and activity impairment are related to accompanying improvements in clinical outcomes. RESULTS: At baseline, 91 of 137 patients (66%) were employed which remained stable throughout the follow-up period. Patients in the working age category were younger and had significantly better asthma control (p = 0.02). Mean overall work impairment due to health decreased significantly from 25.5% (SD2.6) to 17.6% (SD 2.8) during 12 months anti-IL-5/5Ra biologics treatment (P = 0.010). There was a significant association between ACQ6 and overall work improvement after targeted therapy (ß = 8.7, CI 2.1-15.4, P = 0.01). The improvement of asthma control of 0.5 points on the asthma Control Questionnaire was associated with an overall work impairment of -9%. CONCLUSIONS: Work productivity and activity in severe eosinophilic asthma improved after starting anti-IL-5/5Ra biologics. Clinically relevant improvement in asthma control was associated with an overall work impairment score of -9% in this study.

[Joining forces for quality improvement in tuberculosis control]. / Krachten bundelen voor betere tuberculosebestrijding.

The incidence of tuberculosis (TB) in the Netherlands is declining every year. We fear there may be a loss of knowledge and awareness of detecting TB in the new generation of medical specialists. As medical specialists a great challenge lies before us in maintaining the quality of TB control in the Netherlands. Collaboration between pulmonologist, infectious disease specialist, microbiologist and the public health services is a necessity. Here we describe how, in the region of Arnhem, we work closely with these medical specialists based on structural multidisciplinary meetings. We also describe two of the quality indicators - doctor's delay and HIV testing policy - which are included in the national plan for TB control for 2016-2020. We explain how we intend to maintain and improve the quality of TB control by means of our structural meetings and collaboration.

[Acute respiratory failure caused by minocycline]. / Acuut respiratoir falen door minocycline.

BACKGROUND: In the case of pneumonia an infectious cause is always considered first. However, toxic agents and medicines can also be the cause of pneumonia. CASE DESCRIPTION: A 54-year-old woman was referred to the emergency department because of progressive dyspnoea, a non-productive cough, headache, and fever. She was admitted with the diagnosis community acquired pneumonia. Despite treatment with antibiotics and oxygen she developed hypoxic respiratory failure, which necessitated invasive mechanical ventilation. Imaging diagnostics showed extensive bilateral pulmonary consolidation, despite the absence of a causative agent in cultures. Further medical history-taking revealed that the patient had recently commenced a course of minocycline. She had used this medicine previously and had twice before developed pneumonia without the presence of a proven causative agent. Our differential diagnosis included the toxic effect of minocycline and we treated the patient with methylprednisolone. This resulted in rapid clinical improvement and full recovery of our patient. CONCLUSION: Acute respiratory failure as a side effect of medication is rare, but nonetheless potentially life-threatening. Despite repeated exposure to minocycline, the link with pneumonia was not previously made in this patient.

Ventilatory and cerebrovascular responses in normocapnic and hypercapnic COPD patients.

This study investigated the hypothesis that hypercapnia in some chronic obstructive pulmonary disease (COPD) patients may be related to a high cerebrovascular response to carbon dioxide (CO2). The relationship between responses of ventilation and of cerebral blood volume (CBV) to acute changes in carbon dioxide tension in arterial blood (Pa,CO2) was measured in 17 chronic hypercapnic (Pa,CO2 >6.0 kPa) and 16 normocapnic (Pa,CO2 < or = 6.0 kPa) COPD patients, who were matched for degree of airway obstruction (forced expiratory volume in one second 27% predicted). Results were compared with 15 age-matched healthy subjects. CBV was measured using near infrared spectroscopy during normo- and hypercapnia and related to inspired minute ventilation (V'I) and mouth occlusion pressure (P0.1). Hypercapnia (end-tidal pressure of carbon dioxide (deltaPET,CO2) > 1 kPa) was induced by giving adequate amounts of CO2 in the inspired air. During normocapnia, CBV (mL x 100 g(-1)) was 2.41+/- 0.66 and 2.90 +/- 0.60 (mean +/- SD) in the normocapnic and chronic hypercapnic patients, respectively, which was significantly lower compared to healthy subjects (3.53 +/- 0.77). All slopes of CO2 responsiveness (deltaCBV/deltaPa,CO2, deltaV'I/deltaPa,CO2, deltaP0.1/deltaPa,CO2) were significantly lower in both COPD groups relative to healthy subjects, but were not significantly different between the COPD groups. A poor but positive correlation between ventilatory and cerebrovascular CO2 responsiveness (deltaCBV/deltaPa,CO2 and deltaV'I/deltaPa,CO2) was found in COPD patients and healthy subjects. The findings do not support the hypothesis of abnormal cerebrovascular responses to carbon dioxide in hypercapnic chronic obstructive pulmonary disease patients.

Can cerebral blood volume be measured reproducibly with an improved near infrared spectroscopy system?

In some circumstances, cerebral blood volume (CBV) can be used as a measure for cerebral blood flow. A new near infrared spectroscope was used for determining the reproducibility of CBV measurements assessed by the O2-method. Twenty-seven healthy subjects were investigated. An intrasubject coefficient of variation (CV) was calculated, based on four identical episodes of desaturation-resaturation (O2-method) procedures for CBV measurements. Two trials were performed, with (trial 1) and without (trial 2) disconnecting the equipment. A mean CV of 12.6% and 10.0% was found in trial 1 and 2, respectively. Cerebral blood volume values yield 3.60+/-0.82 mL 100 g(-1). Cerebral blood volume could be measured reproducible in adults using near infrared spectroscopy, if the arterial desaturation is limited to approximately 5% from baseline level.

Ventilatory response in metabolic acidosis and cerebral blood volume in humans.

The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (56+/-10 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl) was given orally. CBV was measured using Near Infrared Spectroscopy during normo- and hypercapnia and related to inspired ventilation (V(i)). A mean acute metabolic acidosis of Delta pH - 0.04 was realized with a mean decreased arterialized capillary PCO(2) (P(c)CO(2)) of 0.20 kPa (1.5 mmHg) (both P<0.001). During normocapnia, CBV was 3.51+/-0.71 and 3.65+/-0.56 ml 100 g(-1) (mean+/-S.D.), measured under neutral metabolic conditions and during acute metabolic acidosis, respectively (ns). Corresponding values of V(i) were 7.6+/-1.4 and 10.0+/-2.4 l min(-1) (P<0.01), respectively. The slopes of the CO(2)-responsiveness (DeltaCBV/DeltaP(c)CO(2) and DeltaV(i)/DeltaP(c)CO(2)), were not significantly different during both metabolic conditions. A significant correlation between DeltaCBV/DeltaP(c)CO(2) and DeltaV(i)/DeltaP(c)CO(2) was found during metabolic acidosis (P<0.01), but not under neutral metabolic conditions. CBV does not contribute in a predictable way to the regulation of central chemoreceptors.

Induction of acute metabolic acid/base changes in humans.

The aim of this study was to induce acute metabolic acid/base changes of > or = 2 mequiv.l-1 change in base excess (BE) to aid future investigations of respiratory parameters under these conditions. Ammonium chloride (NH4Cl) was administered to induce acidification and furosemide was used to induce alkalization. Nine healthy volunteers (six men and three women aged 35 +/- 18 years) ingested a calculated amount of NH4Cl at t = 0 and a repeat dose after 60 min. Eight healthy volunteers (three men and five women aged 37 +/- 16 years) consumed 40 mg of furosemide. Arterialized capillary blood gases were measured at t = 0, 30, 60, 90, 120 and 180 min. In the case of acute metabolic acidosis, the target acidification of 2 mequiv.l-1 was attained after 30 min and the greatest change was achieved at 90 min: -4.9 (2.2) mequiv.l-1. In the case of acute metabolic alkalosis, the target alkalization of 2 mequiv.l-1 was reached between 120 and 180 min and the greatest change was seen at 180 min: +2.2 (1.4) mequiv.l-1. Significant (P < 0.05) changes in acidification compared with baseline BE values were found between 60 and 180 min; significant (P < 0.05) changes in alkalization were found between 120 and 150 min. PaCO2 did not change significantly in either condition. We conclude that NH4Cl and furosemide induce a steady state of pure metabolic acid/base conditions in humans, which is buffered in an isocapnic manner.

[Idiopathic CD4(+)-T-lymphocytopenia]. / Idiopathische CD4(+)-T-lymfocytopenie.

Three patients, two men aged 27 and 33 years and one woman aged 31 years, developed several opportunistic infections without presence of HIV infection. Patient A died after suffering Candida stomatitis, extrapulmonary Mycobacterium avium infection, cytomegalovirus infection and Aspergillus pneumonia; patient B recovered from a disseminated M. kansasii infection; patient C suffered from verrucae planae. These patients had CD4(+)-T lymphocytopenia, a shortage of helper T cells. Idiopathic CD4(+)-T lymphocytopenia is a heterogeneous pathological condition with normal serum immunoglobulin concentrations. Treatment consists of combating and preventing infections.