Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Asthma Programme in Finland: Did the use of secondary care resources become more rational?

OBJECTIVES: The aims were to evaluate the profile of newly diagnosed adult asthma cases and the approach adopted to the secondary care management at the launch of the Finnish asthma programme in 1994 and seven years later, in 2001. METHODS: A retrospective medical record audit was made of non-acutely referred patients with asthma in 1994 (n=165) and in 2001 (n=133). Clinical profile data, numbers of out-patient visits and periods of in-patient care before and after asthma diagnosis were gathered from referral letters and secondary care records. RESULTS: The newly diagnosed asthma patients in 2001 were older, more obese and had more co-morbidities. The main asthma symptoms, such as dyspnoea, wheezing and cough, occurred equally in both years but were more often periodic than daily in 2001. Wheezing during auscultation was significantly less common in 2001. The diagnostic process was associated to a history of asthma in first-degree relatives (OR 5.34, 95% CI 1.12-24.49) in 1994 and a visit to a nurse prior to that to a physician (OR 3.13, 95% CI 1.17-8.37) in 2001. Secondary care visits per new case of asthma (7.3 in 1994 vs. 5.4 in 2001) and days in hospital (3.6 in 1994 vs. 0.95 in 2001) decreased significantly. CONCLUSIONS: The profile of asthma diagnosed in secondary care indicates milder disease with more co-morbidities in 2001 than in 1994.Trends towards assigning a more active role on the part of primary care physicians and more rational use of secondary care resources in the management of asthma were found.

Feasibility test results of the Practical Approach to Lung Health in Bishkek, Kyrgyzstan.

SETTING: Ambulatory health centres in Bishkek, Kyrgyzstan. OBJECTIVE: To assess the results of training family doctors in Practical Approach to Lung Health (PAL) techniques. DESIGN: Comparison of the results of two surveys, before (baseline) and after (impact) training on PAL guidelines. Both surveys were carried out according to the same protocol. RESULTS: A total of 86 family physicians working in three ambulatory health centres participated in both surveys. Respectively 893 and 992 respiratory patients were registered in the baseline and impact surveys. Baseline survey patients had longer duration of symptoms, were older and had more concomitant health conditions than impact survey patients. Findings suggest that PAL training has resulted in a decrease by one third in referrals to hospital or specialists or for diagnostic tests. Data do not show any improvement in tuberculosis case detection. However, in the impact survey, the number of drugs prescribed per patient decreased by 13.6% and the average cost of prescription of any drug per patient was reduced by 32.2%. CONCLUSION: The study suggests that training in standardised PAL guidelines is likely to reduce referral as well as drug prescription costs for respiratory patients. These findings need to be confirmed by further studies.

Development process of the Practical Approach to Lung Health in Kyrgyzstan.

The Practical Approach to Lung Health (PAL) strategy was adopted by the Ministry of Health of Kyrgyzstan to improve the quality of case management of priority respiratory illnesses, including tuberculosis (TB). The process of development and implementation of the strategy is described in the present study. The World Health Organization stepwise framework was adapted and used to initiate the PAL strategy within the Kyrgyzstan primary health care (PHC) system. The process followed 10 steps which included the government decision to support PAL development, and the establishment of a national working group in charge of adapting guidelines, developing training materials and testing the feasibility and impact of the guidelines. On the basis of the test results, the guidelines and training materials were revised and a national PAL implementation plan was developed. The ongoing health sector reform which focuses, in priority, on strengthening PHC services and the assistance from the government of Finland, generated favourable political, technical and financial circumstances for the development and implementation of the PAL strategy.

A 10 year asthma programme in Finland: major change for the better.

BACKGROUND: A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society. METHODS: The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti-inflammatory treatment from the outset. The key for implementation was an effective network of asthma-responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini-Programme was launched. RESULTS: The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were 218 million euro which had fallen to 213.5 million euro in 2003. Costs per patient per year have decreased 36% (from 1611 euro to 1031 euro). CONCLUSION: It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.

The asthma programme of Finland: an evaluation survey in primary health care.

OBJECTIVE: To evaluate the basic structures and processes of asthma care 6 years after the launch of the Finnish Asthma Programme. The evaluation will serve as the baseline for the implementation of the evidence-based guidelines for asthma published in 2000. DESIGN: A descriptive type-2 evaluation (managerial monitoring of a policy implementation), based on operationalised statements of the Asthma Programme. RESULTS: A co-ordinating doctor for asthma, usually a general practitioner (GP), was interviewed in 248 (91%) health centres; 83% of the health centres have at least one GP nominated as the local asthma co-ordinator and 94% have a nurse. Asthma education for the professionals had been organised in 71% of the health centres in the previous 2 years. First-line treatment consists of an inhaled corticosteroid. Guided self-management is used in 98% of the health centres, but its components were not clear to the doctors. CONCLUSION: The basic structure of equipment and organisation for the diagnosis and treatment of asthma has been set up in the primary health care services.

Effects of surgical removal of lung cancer on total plasma antioxidant capacity in lung cancer patients.

Previous evidence suggests that malignant tumors cause an oxidative burden to human antioxidative defense systems. We followed the plasma total radical-trapping antioxidant parameters (TRAP) and their main antioxidant components (alpha-tocopherol, uric acid, protein sulfhydryl groups, and unidentified antioxidant proportions) in 13 lung cancer patients and 7 control patients scheduled for thoracotomy. Plasma samples were collected 9 times during a 5 month follow-up period in the cancer patients. The objective of the study was to evaluate the effects of surgical removal of lung cancer on human plasma total antioxidant capacity. A significant reduction of plasma TRAP (period effect of ANOVA, p = 0.0006) and its components appeared in both groups during the first postoperative day. This decrease was due to reduction of ascorbate (p = 0.002) alpha-tocopherol (p = 0.0001) and urate (p = 0.05) concentrations. At 3 and 5 months after the surgical removal of the tumor there was an augmentation in plasma TRAP concentrations (p = 0.02, 3 months; p = 0.07, 5 months). This was mainly due to the increases in plasma yet as unidentified antioxidant components (UNID) and protein SH-groups. The data indicates that, first, thoracotomy itself causes a reduction in plasma TRAP during the early hours after operation, and secondly surgical removal of lung cancer increases plasma TRAP concentrations compared to the baseline values possibly reflecting the relief of oxidative stress caused by malignant tumors.

Human plasma antioxidant capacity during radiotherapy for lung cancer: a clinical study.

Even though it is well established that oxygen-free radicals are the main mechanism responsible for the cytotoxicity produced during radiotherapy, the role of the human antioxidant defense system in clinical radiation oncology is still to be clarified. Changes in the human plasma total peroxyl radical trapping capacity (TRAP) and its individual components were followed during clinical radiotherapy for lung cancer. Sixteen patients receiving radical-aimed radiotherapy provided blood samples nine times during the treatment. Our hypothesis was that oxygen-free radical production increased by irradiation should decrease the plasma TRAP as a consequence of oxidative stress. Only a moderate reduction of the plasma TRAP was found during the therapy in the study group taken as a whole, but the development pattern of TRAP and its unidentified components were clearly different in those patients showing complete or partial response to the treatment and those in which the disease progressed unabated. Plasma ascorbate levels showed no significant changes during radiotherapy. A decrease in vitamin E concentrations was seen after 6 Gy (p=0.05). Uric acid concentrations increased towards the end of the radiotherapy in both response groups (p=0.02 at 50 Gy). In this study, 26.6% of the plasma TRAP was due to unidentified antioxidants (UNID).

Assay of antioxidant capacity of human plasma and CSF in aging and disease.

Oxidative damage to DNA and other macromolecules accumulates with age and has been postulated to be one of the major forms of endogenous damage leading to aging and has been implicated also in initiation of cancer and over a hundred other diseases. The human body has developed an antioxidant (AOX) defense system which contains enzymatic, metal chelating, and free radical scavenging properties. Thus, it is essential to consider the concentration of all AOXs in plasma and CSF when investigating the relationship between diet, oxidative stress, and disease. In the present study a luminometric TRAP-method (total peroxyl radical-trapping potential) was used to determine the activity of all chain breaking AOXs in several clinical states. We have measured TRAP of plasma, cerebrospinal fluid (CSF) and of low density lipoprotein (LDL, TRAPLDL), and the concentrations of main AOX-components (uric acid, protein SH-groups, alpha-tocopherol, ascorbic acid, ubiquinone and the fraction of unknown antioxidants) to study the effect of: 1) aging, 2) acute infection, 3) diabetes, 4) immobilization and 5) cancer. TRAP of CSF is five times lower than of plasma, mainly due to the low urate concentration in CSF. We have observed that plasma antioxidant defenses respond to the basic metabolic rate and the challenges caused by physiological or pathological stress: i) in a healthy normal population TRAP and TRAPLDL change with age and a substantial proportion of TRAP cannot be attributed to any known AOXs thus indicating the existence of unmeasured an unidentified antioxidant(s); ii) during acute infection and immobilization the exogenous AOXs (vitamin C and E) remained unchanged, whereas the activity of unidentified AOXs of plasma declined sharply; iii) in those NIDDM patients with coronary heart disease plasma TRAP is reduced. In conclusion, TRAP has revealed important information for evaluating the AOX status of human plasma, CSF and LDL. According to our studies, important, possibly endogenous AOXs still remain to be identified.

Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment.

Ratios of urinary 8-hydroxy-2'-deoxyguanosine to urinary creatinine (8-OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation. Urinary 8-OHdG/creatinine levels of lung cancer patients were evaluated by enzyme-linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy. An increase in urinary 8-OHdG/creatinine was found in non-small-cell carcinoma (non-SCC) patients during the course of radiotherapy. SCC patients showed higher levels of urinary 8-OHdG/creatinine than the controls. Furthermore, SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8-OHdG/creatinine while patients with no change or progressive disease showed an increase.

Plasma peroxyl radical trapping capacity in lung cancer patients: a case-control study.

Increasing evidence suggests that cancer patients express oxidative disturbances. The main objective of this cross-sectional case-control study (n = 57 + 76) was to explore whether lung cancer patients, when compared to healthy controls, have alterations in their plasma peroxyl radical trapping capacity (TRAP). Group matching was used with respect to age, sex and smoking history. A secondary objective was to observe the effects of life-long cigarette consumption on plasma TRAP and its components. Mean TRAP values were significantly lower in the cancer patients than in the control group (1143 vs 1273 mumol/l, p = 0.0002). Moreover, all the components of TRAP (except uric acid) were significantly lower in the cancer group: protein SH-groups 442 vs 571 mumol/l, ascorbic acid 34.0 vs 46.5 mumol/l and vitamin E 25.0 vs 33.8 mumol/l. The as yet unidentified antioxidant compounds in plasma contributed 26.5% of plasma TRAP in the cancer group and 30.2% in the control group. There was no correlation between cigarette consumption in pack-years and plasma TRAP; however, plasma concentrations of uric acid and ascorbic acid were negatively correlated with cigarette consumption.

Effects of anthracyclin-based chemotherapy on total plasma antioxidant capacity in small cell lung cancer patients.

Plasma total peroxyl radical trapping antioxidant parameters (TRAP) and their main antioxidant components (vitamin E, uric acid, protein sulfhydryl groups, and unidentified antioxidant proportions) were measured in 12 small cell lung cancer (SCLC) patients receiving combined chemotherapy consisting of vincristine, adriamycin and cyclophosphamide for SCLC. Plasma samples were collected ten times during the first two cycles of chemotherapy. There is previous evidence that many anticancer drugs exert their cytotoxity via free oxygen radicals. We hypothesized that adriamycin-induced, increased oxygen free radical production should decrease plasma TRAP as a consequence of oxidative stress. A statistically significant reduction of plasma TRAP was noted 8 hours after the first adriamycin infusion. A reduction of calculated TRAP (TRAPcalc)--the sum of concentrations of individual antioxidants, corrected by their experimentally-determined stochiometric factors--appeared 3 hours after the first adriamycin infusion and continued for up to 1 week afterwards. This decrease was due to the reduction of ascorbate and urate concentrations. Total TRAP, however, recovered to initial levels after 200 hours, due to an increase in unidentified antioxidants. The second course of adriamycin. These results are in accordance with previous studies showing the formation of oxidants with the use of anthracyclines. Evidence suggests that the as yet unidentified component of TRAP (UNID) increases during the oxidative stress caused by anthracycline based chemotherapy.