[MITRA-FR and COAPT : Why are the results so different and what are the consequences for the daily routine?] / MITRA-FR und COAPT : Warum sind die Ergebnisse so unterschiedlich, und welche Konsequenzen ergeben sich für den Alltag?

Percutaneous mitral valve repair with the MitraClip in the COAPT study significantly reduced overall mortality and hospitalization in patients with at least moderate to severe mitral valve regurgitation, in comparison to guideline-compliant drug treatment alone. Consequently, the assumption that secondary mitral regurgitation is more a consequence than the cause of systolic heart failure needs to be revised; however, data from the simultaneously published MITRA-FR study showed no prognostic benefits for patients with advanced heart failure and severely enlarged left ventricle; therefore, MitraClip treatment should only be performed after careful patient selection and heart team decision. With respect to future patient selection further studies are needed to better define cut-offs for treatment or exclusion criteria and to identify patients who profit the most from treatment. Also, new catheter-based techniques and alternative approaches to treat functional mitral regurgitation need to be investigated.

Time trends (2006-2015) of quality indicators in EUSOMA-certified breast centres.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. MATERIALS AND METHODS: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. RESULTS: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. CONCLUSION: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.

Evaluation of Iron Deficiency Using Reticulocyte Indices in Dogs Enrolled in a Blood Donor Program.

BACKGROUND: People donating blood more than twice annually are at risk of developing iron deficiency. Little is known about the iron status of dogs enrolled in blood donor programs. HYPOTHESIS: Dogs donating blood ≥6 times annually will show evidence of iron deficiency based on their reticulocyte indices. ANIMALS: Thirteen dogs enrolled in a blood donor program donating ≥6 times over the preceding 12 months and 20 healthy nondonor control dogs. METHODS: Prospective observational study. Mature red blood cell (RBC) indices, reticulocyte indices, serum iron, serum ferritin, and total iron-binding capacity (TIBC) were compared between groups. RESULTS: Packed cell volume (median 47%, range 40-52%, P < .01), hematocrit (median 46.4%, range 40.3-52.5%, P < .01), and reticulocyte count (median 16,000/µL, range 9,000-38,000/µL, P < .01) were significantly lower in the blood donor dogs. No statistically significant differences were noted in the mature RBC indices between groups. Both reticulocyte mean corpuscular volume (median 88.8 fL, range 83.4-95.5 fL, P = .03) and reticulocyte hemoglobin content (median 24.6 pg, range 23.1-26.6 pg, P < .01) were significantly lower in the blood donor group. Serum iron and ferritin were similar between groups; however, TIBC was significantly higher in the control group (median 403 µg/dL, range 225-493 µg/dL, P = .02). CONCLUSIONS: The findings in dogs donating ≥6 times annually suggest the presence of iron-deficient erythropoiesis in this population.

The effect of EUSOMA certification on quality of breast cancer care.

AIM OF THE STUDY: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. MATERIALS AND METHODS: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. RESULTS: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. CONCLUSION: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.

The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use.

BACKGROUND: We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC). PATIENTS AND METHODS: A total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0-3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded. RESULTS: Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice. CONCLUSION: RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.

Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting.

OBJECTIVE: The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. METHODS: A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. RESULTS: The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. LIMITATIONS: Country-specific data on the risk of distant recurrence and quality-of-life were not available. CONCLUSIONS: Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer.

Evaluation of serum ferritin as a tumor marker for canine histiocytic sarcoma.

BACKGROUND: Canine histiocytic sarcoma (HS) is an aggressive malignancy. Hyperferritinemia has been documented in dogs with HS and could serve as a tumor marker aiding in diagnosis and treatment. In people, hyperferritinemia is found in inflammatory diseases, liver disease, and hemolysis, and thus may occur in dogs with these conditions. OBJECTIVE: To determine if serum ferritin concentration is a tumor marker for canine HS. ANIMALS: Dogs with HS (18), inflammatory diseases (20), liver disease (24), immune-mediated hemolytic anemia (IMHA) (15), and lymphoma (23). METHODS: Prospective, observational, cohort study: Serum ferritin concentration was measured at initial diagnosis. Parametric methods were used to compare mean log ferritin concentrations among disease categories. Receiver-operating characteristic curves and likelihood ratios were used to evaluate serum ferritin concentration as a tumor marker. RESULTS: Varying proportions of dogs with IMHA (94%), HS (89%), liver disease (79%), lymphoma (65%), and inflammatory diseases (40%) had hyperferritinemia. Dogs with IMHA had significantly higher mean ferritin concentration than dogs in all other categories. Dogs with HS had significantly higher mean ferritin concentration than those in the inflammatory disease and lymphoma categories. Mean serum ferritin concentration was not significantly different between dogs with HS and those with liver disease. Decision thresholds were determined to distinguish IMHA and HS from the other diseases associated with hyperferritinemia. CONCLUSION: Hyperferritinemia is common in dogs with HS and, after IMHA is ruled out, the degree of hyperferritinemia may be useful in differentiating dogs with HS from dogs with inflammatory diseases, liver disease, and lymphoma.

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients.

The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n = 34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P = 0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n = 54) as compared with controls (n = 44) and disease-free patients (n = 48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy.

Isolation and characterisation of cancer stem cells from canine osteosarcoma.

There is increasing evidence that cancer is a stem cell disease. This study sought to isolate and characterise cancer stem cells from canine osteosarcoma. One human and three canine cell lines were cultured in non-adherent culture conditions using serum-starved, semi-solid media. Primitive sarcosphere colonies from all cell lines were identified under these conditions and were characterised using molecular and cytochemical techniques for embryonic stem cell markers. Expression of the embryonic stem cell-associated genes Nanog, Oct4 and STAT3 indicated a primitive phenotype. Sarcospheres could be reproduced consistently when passaged multiple times and produced adherent cell cultures when returned to normal growth conditions. Similarities between human and canine osteosarcoma cell lines add credence to the potential of the dog as a model for human disease.

HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.

PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.

Combination of taxanes and anthracyclines in first-line chemotherapy of metastatic breast cancer: an interim report.

Anthracyclines and taxanes are among the most effective agents in the treatment of advanced breast cancer, refractory or non-responsive to endocrine manipulation. Several recently published phase III studies have addressed the role of these compounds in combination compared with established chemotherapy regimens. This report considering a total of 4244 patients evaluates the data of those trials with respect to the efficacy and toxicity of the treatment regimens. Currently, evidence is growing that especially patients with symptomatic visceral tumour spread may benefit from the combined application of anthracyclines and taxanes. Adequately dosed polychemotherapy appears to be more successful than monotherapy, and, at present, the combination of anthracyclines (doxorubicin, epirubicin) and taxanes (docetaxel (Doc), paclitaxel (Pac)) might lead to a promising approach to improve the course of the metastatic disease.

[Acute hemorrhage from Meckel's diverticulum--Laparotomy or laparoscopy?]. / Die akute Blutung aus einem Meckel'schen Divertikel - Laparotomie oder Laparoskopie?

Meckel's diverticulum is the most common congenital malformation of the gastrointestinal tract with a potential risk to develop complications such as obstruction, diverticulitis or intussusception. Lower gastrointestinal bleeding due to ulceration of heterotopic gastric tissue of the diverticulum is a known phenomenon in children and young adults. We present two cases of a 15-year-old girl and a 20-year-old man that revealed a massive lower gastrointestinal hemorrhage of unknown origin. In this emergency situation laparotomy was performed in combination with lower endoscopy as rendezvous manouver. In both cases a Meckel's diverticulum with peptic ulceration was the source of hemorrhage, in one case the bleeding was active and visible. After resection of a short small bowel segment and end-to-end anastomosis the postoperative course was uneventful. We prefer in the case of lower gastrointestinal hemorrhage with hemodynamic instability laparotomy with intraoperative endoscopy instead of laparoscopy.

Epidermal barrier lipids in human vernix caseosa: corresponding ceramide pattern in vernix and fetal skin.

BACKGROUND: Vernix caseosa is a protective biofilm covering the fetus during the last trimester. Vernix and epidermal barrier lipids (i.e. cholesterol, free fatty acids and ceramides) appear to share protective functions for fetal and neonatal skin. OBJECTIVES: To analyse vernix samples for epidermal barrier lipid content, and to compare lipid profiles of vernix with those of fetal and postnatal epidermis. METHODS: Vernix samples were collected from 21 healthy term neonates. Skin samples were collected from 10 fetuses aborted between gestational week (GW) 16 and 25, nine infants and 11 older children. Lipids were extracted according to standard protocols and analysed by high-performance thin-layer chromatography. RESULTS: Vernix contained 196.5 +/- 70.1 microg barrier lipids mg-1 protein (mean +/- SD). Cholesterol formed the major barrier lipid fraction (52.8%), followed by free fatty acids (27.7%) and ceramides (20.1%). The ceramide composition of vernix resembled that of mid-gestational (GW 23-25) fetal epidermis both qualitatively and quantitatively, while there were major differences from postnatal epidermis. The total epidermal ceramide concentration increased significantly between prenatal and postnatal samples. CONCLUSIONS: The composition pattern of ceramides mirrors that of mid-gestational fetal epidermis. Vernix thus represents a 'homologous' substitute for the immature epidermal barrier in fetal skin. The differential role of individual ceramides in this process remains to be established.

Surgical management of gastrointestinal stromal tumors of the stomach.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract with varying degree of dignity and prognosis. Intramural or extragastral growth of gastric GISTs is associated with diagnostic difficulties and uncertainty about the type and extent of surgical therapy. Based on our experience, we tried to formulate management guidelines for gastric GISTs. METHODS: Five patients with gastric GIST (36-85 years old) underwent subserosal excision with subsequent B-II resection (1x), full-thickness partial gastric resection (2x), gastrotomy with submucosal excision (1x), or gastrectomy for carcinoma with an incidental finding of a leiomyoma (1x). RESULTS: Tumor size ranged from 2x2x1 cm to 9x6x4 cm. These tumors were classified as epithelioid leiomyosarcoma (1x), GIST (3x), or leiomyoma (1x). The prognosis of risk ranged from no risk (leiomyoma) to low-malignancy (leiomyosarcoma) depending on tumor size and mitotic index. No recurrent disease has been noted so far during follow-up ranging from 3 months to 6 years. CONCLUSIONS: Staging of gastric disease should include the probability of gastric GIST. Surgical resection is the therapy of choice for potential malignant GISTs to ensure a local radical removal. Metachronic metastases should be resected if possible. Depending on tumor stage and prognostic parameters, an individual follow-up with endoscopic and radiologic examinations is recommended. Further studies should be undertaken to elaborate prognostic determinants and stage-adapted treatment.

Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.

PURPOSE: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles. RESULTS: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel. CONCLUSION: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

[Aromatase inhibitors--new possibilities in treatment of breast carcinoma]. / Aromatasehemmer--neue Möglichkeiten in der Behandlung des Mammakarzinoms.

Aromatase inhibition is now an acknowledged second line treatment modality for advanced breast cancer in postmenopausal women. Aminoglutethimide is an inhibitor of adrenal steroid biosynthesis and blocks the conversion of cholesterol to pregnenolone, and therefore reduces levels of adrenal androgens, which are a source of estrogens in both premenopausal and postmenopausal women. Aminoglutethimide has produced antitumor response rates of 35% in unselected patients, most of whom have undergone prior therapy with either chemotherapy or hormonal manipulation. As is true of other hormonal responses, high response rates of up to 70% are observed in patients who are ER and/or PR positive. The reason why these drugs are currently used after tamoxifen is mainly due to the side effects of aminoglutethimide, which impairs the mineralocorticoid and glucocorticoid synthesis. New, less toxic compounds appear, which block the conversion of androstenedione to estrone and efficiently suppress plasma estrogen levels., e.g. formestane, anastrozole and letrozole. Aromatase inhibitors are now being compared to tamoxifen as first-line endocrine treatment in relapsing patients. If these trials confirm a similar or better response rate to new aromatase inhibitors compared to tamoxifen, the time will come to study them as the first line adjuvant treatment in non-metastatic disease.

Airborne particulate matter modulates the production of reactive oxygen species in human polymorphonuclear granulocytes.

Causal relationships between airborne particles (especially particulate matter < 10 microm in diameter) and increases in prevalences and symptoms of respiratory diseases have been postulated in many epidemiologic studies. Polymorphonuclear leukocytes (PMN) in the nasal or bronchial epithelium can be exposed to particulate matter (PM) and may upon exposure produce reactive oxygen species (ROS). Release of ROS can result in cellular and tissue damage and initiate or exacerbate inflammation. To elucidate the effect of PM on inflammatory reactions, we exposed human PMN to PM extracts. PM were collected with high volume samplers in two cities, Dusseldorf and Duisburg, in Germany and reflect sites with high traffic and industrial emissions respectively. The collected particles were extracted using water and then dichloromethane, resulting in an aqueous and an organic extract. The production of ROS was determined using luminol-enhanced chemiluminescence (LCL) of resting and zymosan-stimulated PMN. The present study shows that extracts of PM alone significantly stimulated the production and release of ROS in resting PMN. The effects of the PM extracts were inhibited by superoxide dismutase (SOD), catalase and sodium azide (NaN3). Zymosan-induced LCL was, however, diminished by coincubation with PM extracts. The chemical composition is important when considering the effects of particles. Our study shows that only organic substances adsorbed to particles stimulate LCL. SOZ-induced LCL is inhibited by both types of extracts, but aqueous extracts have a stronger inhibitory effect. It is at present unclear which substances are responsible for these effects.

Air pollution and allergy: experimental studies on modulation of allergen release from pollen by air pollutants.

The fact that allergic diseases increase in prevalence is a generally accepted and worldwide phenomenon. The causes for this increase are not known: only hypothetical concepts exist. Epidemiological studies comparing Eastern and Western European populations have shown a striking difference in the prevalence of respiratory atopic diseases, which is lower in the East. At the same time, different patterns of air pollution have been described, namely 'classical' type I, characterized by SO2 and dust prevailing in the East, and 'modern' type II, characterized by organic compounds, fine particles and ozone, which is more prominent in the West. Type II was associated in multivariate regression analysis with increased prevalence of IgE-mediated allergy. Pollen grains collected from industrial regions with high polyaromatic hydrocarbon load in West Germany, but not in East Germany, were shown to be agglomerated with airborne particles. In vitro exposure of pollen to particles indicated morphological changes and increased allergen release from the pollen. In vitro exposure of pollen to gaseous pollutants (SO2 and NO2) under different conditions of humidity resulted in SO2-induced, but not NO2-induced reduction of allergen release from pollen. It is concluded that the bioavailability of grass pollen allergens may be modulated by air pollutants, supporting the concept of an interaction between pollen and pollutants in the atmosphere outside the organism which in turn may affect allergy-relevant phenomena.