Jaro Ankerst

Basophil allergen threshold sensitivity: a useful approach to anti-IgE treatment efficacy evaluation

Background:  Monitoring of the allergen sensitivity of a patient is most important for optimal patient care and a basic prerequisite for immunomodulating treatment. The objective of this study was to investigate how basophil allergen sensitivity can be applied in the monitoring of anti‐immunoglobulin E (IgE) treatment.

After 6 years with Xolair; a 3-year withdrawal follow-up

Background:  This study reports the clinical and immunological state of patients 3 years after a 6‐year period of Xolair treatment for severe allergic asthma.

CD-sens and clinical changes during withdrawal of Xolair after 6 years of treatment

Background:  Many clinical trials with omalizumab, Xolair, have been reported but the treatment period has always been short, i.e. <12 months. After withdrawal, the clinical symptoms tend to return. A group of patients who stopped treatment after approx. 6 years allowed studies of the long‐term effects of Xolair.

Laser-Induced Fluorescence Studies of Hematoporphyrin Derivative (HPD) in Normal and Tumor Tissue of Rat

Fluorescence studies of hematoporphyrin derivative (HPD) in normal and tumor tissue of rat were performed with nitrogen laser excitation and optical multi-channel detection. Fifteen types of tissue including inoculated tumor were investigated for rats at different delays after HPD injection. Optimum contrast functions and other criteria for discriminating tumor tissue from normal tissue are discussed. The results should have implications for practical human HPD endoscopy.

Tolerability of a high dose of budesonide/formoterol in a single inhaler in patients with asthma

This randomised, double-blind, double-dummy, crossover, placebo-controlled study assessed the acute tolerability of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler, AstraZeneca) administered as a high dose. Fourteen patients with asthma receiving budesonide/formoterol maintenance treatment (two inhalations of 160/4.5 microg twice daily) inhaled 10 additional doses of budesonide/formoterol 1600/45 microg (total daily dose including morning dose of maintenance treatment 1920/54 microg) or formoterol 45 microg (Oxis Turbuhaler, AstraZeneca; total daily dose including morning dose of maintenance treatment 54 microg formoterol) or placebo in addition to the morning dose of maintenance treatment on 3 separate study days. Serum potassium, pulse rate, blood pressure and ECG were assessed at regular intervals over a 12-h period following dosing. Blood glucose and plasma lactate were assessed over 3 h following dosing. Changes in serum potassium, pulse rate, blood pressure, QTc, blood glucose and plasma lactate occurring with budesonide/formoterol, though statistically significantly different from placebo (P<0.05), were considered clinically unimportant. No clinically relevant differences were identified between active treatments. In conclusion, budesonide/formoterol in a single inhaler is well tolerated at high doses such as might be used by patients using budesonide/formoterol for relief of symptoms of asthma.

LASER‐INDUCED FLUORESCENCE IN MALIGNANT and NORMAL TISSUE OF RATS INJECTED WITH BENZOPORPHYRIN DERIVATIVE

Abstract— Laser‐induced fluorescence was used to characterize the localization of intravenously administered ben‐zoporphyrin derivative‐monoacid (BPD‐MA) 3 h postinjection in different rat tissue types, including an induced experimental malignant tumor. A comparison of the fluorescence properties and the demarcation potential between the newer sensitizer BPD‐MA and four other substances, hematoporphyrin (HP), polyhematoporphyrin ester (PHE), tetrasulfonated phthalocyanine (TSPc) and the commercially available Photofrin earlier investigated, is included. The fluorescence light was induced with a nitrogen laser, emitting at 337 nm. The fluorescence spectrum in the region380–750 nm was analyzed by a polychromator equipped with a diode array detector. The demarcation potential between tumor and surrounding tissue in terms of fluorescence signal for the tumor model used was 2:1 for BPD‐MA. In comparison with the other drugs, HP shows about the same demarcation potential, whereas Photofrin and PHE exhibit about 3 times better and TSPc about 1.5 times better demarcation. By also employing the endogenous tissue fluorescence signature the contrast was enhanced by a factor of about 2 for each of the five drugs.

Circulating eosinophils in asthma, allergic rhinitis, and atopic dermatitis lack morphological signs of degranulation.

Background In allergic diseases, eosinophils in affected tissues release granule proteins with cytotoxic, immunoregulatory, and remodelling‐promoting properties. From recent observations, it may be assumed that eosinophils degranulate already in circulating blood. If degranulation occurs in the circulation, this could contribute to widespread systemic effects and provide an important marker of disease.

Tumour marking properties of different haematoporphyrins and tetrasulfonated phthalocyanine - A comparison

Several photosensitizers were screened for their tumour-marking ability using laserinduced fluorescence in Wistar/Furth rats bearing subcutaneous adenocarcinomas inoculated in muscle. Of the studied photosensitizers, dihaematoporphyrin ether appeared to exhibit the best tumour-demarcation properties. Polyhaematoporphyrin ester and tetrasulfonated phthalocyanine were almost as good although the fluorescence yield was much lower. Monomeric haematoporphyrin also showed some tumour-marking qualities. By forming fluorescence intensity ratios, information from both the blue and the red spectral regions were used to provide the highest tumour-to-muscle contrast. Two excitation wavelengths were used, of which 337 nm rather than 405 nm excitation light seemed to yield a better tumour demarcation, due to a greater difference in the superimposing autofluorescence between tumour and surrounding tissue. The study included measurements on many inner organs in an attempt to gain a better understanding of the interaction between the drugs and various kinds of tissue.

Pharmacokinetics of Budesonide and Formoterol Administered Via 1 Pressurized Metered-Dose Inhaler in Patients With Asthma and COPD

In 3 open‐label studies, the systemic bioavailability of budesonide and formoterol administered via pressurized metered‐dose inhaler (pMDI) or dry powder inhaler (DPI) formulations was evaluated in asthma (24 children, 55 adults) or chronic obstructive pulmonary disease (COPD; n =26) patients. Treatments were administered at doses high enough to estimate pharmacokinetic parameters reliably. Two of the studies included an experimental budesonide pMDI formulation. In study 1 (asthma, adults), budesonide area under the curve (AUC) was 32% and 31% lower and maximal budesonide concentration (Cmax) 45% and 56% lower after budesonide/formoterol pMDI and budesonide pMDI versus budesonide DPI. Formoterol AUC and Cmax were 13% and 39% lower after budesonide/formoterol pMDI versus formoterol DPI. In study 2 (asthma, children), budesonide AUC and Cmax were 27% and 41% lower after budesonide/formoterol pMDI versus budesonide DPI + formoterol DPI. In study 3 (COPD/asthma, adults), budesonide AUC and Cmax were similar and formoterol AUC and Cmax 18% and 22% greater after budesonide/formoterol pMDI versus budesonide pMDI + formoterol DPI (COPD). Budesonide and formoterol AUC were 12% and 15% higher in COPD versus asthma patients. In conclusion, systemic exposure generally is similar or lower with budesonide/formoterol pMDI versus combination therapy via separate DPIs or monotherapy and comparable between asthma and COPD patients.

Flow-Volume Parameters in COPD Related to Extended Measurements of Lung Volume, Diffusion, and Resistance

Classification of COPD into different GOLD stages is based on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) but has shown to be of limited value. The aim of the study was to relate spirometry values to more advanced measures of lung function in COPD patients compared to healthy smokers. The lung function of 65 COPD patients and 34 healthy smokers was investigated using flow-volume spirometry, body plethysmography, single breath helium dilution with CO-diffusion, and impulse oscillometry. All lung function parameters, measured by body plethysmography, CO-diffusion, and impulse oscillometry, were increasingly affected through increasing GOLD stage but did not correlate with FEV1 within any GOLD stage. In contrast, they correlated fairly well with FVC%p, FEV1/FVC, and inspiratory capacity. Residual volume (RV) measured by body plethysmography increased through GOLD stages, while RV measured by helium dilution decreased. The difference between these RV provided valuable additional information and correlated with most other lung function parameters measured by body plethysmography and CO-diffusion. Airway resistance measured by body plethysmography and impulse oscillometry correlated within COPD stages. Different lung function parameters are of importance in COPD, and a thorough patient characterization is important to understand the disease.