Global strategy for asthma management and prevention

This document is an international evidence-based guideline on the diagnosis and management of idiopathic pulmonary fibrosis, and is a collaborative effort of the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society, and the Latin American Thoracic Association. It represents the current state of knowledge regarding idiopathic pulmonary fibrosis (IPF), and contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For the diagnosis and treatment sections, pragmatic GRADE evidence-based methodology was applied in a question-based format. For each diagnosis and treatment question, the committee graded the quality of the evidence available (high, moderate, low, or very low), and made a recommendation (yes or no, strong or weak). Recommendations were based on majority vote. It is emphasized that clinicians must spend adequate time with patients to discuss patients' values and preferences and decide on the appropriate course of action.

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-Based Guidelines for Diagnosis and Management

Lung volumes are subdivided into static and dynamic lung volumes. Static lung volumes are measured by methods which are based on the completeness of respiratory manoeuvres, so that the velocity of the manoeuvres should be adjusted accordingly. The measurements taken during fast breathing movements are described as dynamic lung volumes and as forced inspiratory and expiratory flows.

### 1.1 Static lung volumes and capacities

The volume of gas in the lung and intrathoracic airways is determined by the properties of lung parenchyma and surrounding organs and tissues, surface tension, the force exerted by respiratory muscles, by lung reflexes and by the properties of airways. The gas volumes of thorax and lung are the same except in the case of a pneumothorax. If two or more subdivisions of the total lung capacity are taken together, the sum of the constituent volumes is described as a lung capacity. Lung volumes and capacities are described in more detail in § 2.

#### 1.1.1 Determinants

Factors which determine the size of the normal lung include stature, age, sex, body mass, posture, habitus, ethnic group, reflex factors and daily activity pattern. The level of maximal inspiration (total lung capacity, TLC) is influenced by the force developed by the inspiratory muscles (disorders include e.g. muscular dystrophy), the elastic recoil of the lung (disorders include e.g. pulmonary fibrosis and emphysema) and the elastic properties of the thorax and adjacent structures (disorders include e.g. ankylosis of joints). The level of maximal expiration (residual volume, RV) is determined by the force exerted by respiratory muscles (disorders include e.g. muscle paralysis), obstruction, occlusion and compression of small airways (disorders include e.g. emphysema) and by the mechanical properties of lung and thorax (disorders include diffuse fibrosis, kyphoscoliosis).

Assessing the total lung capacity is indispensable in establishing a restrictive ventilatory defect or in diagnosing abnormal lung distensibility, as may occur in patients …

Lung volumes and forced ventilatory flows

Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.

The Effects of Plant Flavonoids on Mammalian Cells:Implications for Inflammation, Heart Disease, and Cancer

Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

/pdf/allergic-rhinitis-and-its-impact-on-asthma-20b4c7y0pr.pdf

Allergic Rhinitis and Its Impact on Asthma

The bronchodilating effect of 5 mg sublingual isosorbide dinitrate (ISDN) was studied in 10 patients with bronchial asthma, using the double-blind randomised cross-over method with matched placebo. In a further 20 asthmatics the effect of sublingual ISDN was compared with that of metaproterenol given by a metered dose inhaler to a total dose of 2.25 mg, again using the cross-over method. The forced oscillation method was used to measure respiratory resistance (Rrs) and spirometry was used to measure vital capacity (VC) and forced expiratory volume in one second (FEV1). 5 minutes after administration of ISDN Rrs had decreased (p less than 0.05) and VC (p less than 0.01) and FEV1 (p less than 0.01) were significantly increased. The changes were still present after 15, 30 and 60 min. The placebo had no significant effect. ISDN increased FEV1 less than metaproterenol, and the difference between them was statistically significant (p less than 0.05). However, there was no significant difference between ISDN and metaproterenol in the improvement in Rrs and VC. Of the total of 30 patients, 11 experienced headache and 4 had transient hypotension after ISDN administration. These side effects subsided spontaneously. It was concluded that sublingual ISDN had a bronchodilating effect in stable asthmatics.

Bronchodilator effect of sublingual isosorbide dinitrate in asthma.

The lung tissue of pulmonary alveolar microlithiasis was studied morphologically. Scanning electron microscopy revealed that the microliths were globular or irregular in shape or lobulated and in some loci were coalesced. The outer surface was granular or rough accompanied with deposits. The internal structures consisted of concentric laminar deposits. Frequently, two or more laminar structures were found on one cut surface. These findings may imply that the microliths grow by surface deposition and may coalesce during early stages of formation. In a high power view, granules were seen on the surface. Numerous scale-like structures and elongated electron-dense bodies inside the microliths were other peculiar findings of scanning and transmission electron microscopic studies, respectively. Elastosis in the alveolar interstitium and deposition of abundant glycogen granules in the bronchiolar epithelial cells were the notable findings of transmission electron microscopy.

Electron microscopic studies on pulmonary alveolar microlithiasis.

Electron microscopic observations were made on lung tissue, broncho-pulmonary lavage fluid and sputum in 2 cases of pulmonary alveolar proteinosis. Diagnosis was established by open lung biopsy in both cases. In Case 1 the electron microscopic samples were obtained from the surgical specimen. In Case 2 an electron microscopic observation was made only on the lavage fluid and sputum. The alveolar air spaces were full of amorphous or fine granular-appearing material intermingled with two kinds of laminated bodies (abbreviated to "Lamella A" and "Lamella B"). Lamella A, about 0.2 approximately 4 micrometer in diameter, presented a concentric laminated structure with approximately 300 A periodicity and was found in the alveolar air spaces, lung washings and sputum. It corresponded to what has hitherto been reported in the same disease and was always located outside the cells. Lamella B showed a laminated structure of high electron density, approximately 50 A in periodicity, usually looking like a concentric circle with a diameter of 0.5 micrometer or less. It was intensely stained with methenamine silver. It was mainly observed in mesenchymal cells of the alveolar septa and free macrophages in the alveolar air spaces, although it also occurred in the type I and type II alveolar epithelial cells. Furthermore, the Lamella B could be found in the alveolar air spaces outside the cells and in the bronchopulmonary lavage fluid. This body has not been demonstrated previously and, although its significance in this disease is still uncertain, the structural similarity of the Lamella B to the intra-alveolar material suggests a possible role of it in the production of intra-alveolar material.

A new myelin-like laminated body found in two cases of pulmonary alveolar proteinosis.

Surfactant apoprotein-A concentration in sputum for diagnosis of pulmonary alveolar proteinosis.

A therapy consisting of a combination of an anticoagulant and a vasodilator was investigated to determine its effects on the long-term prognosis of primary pulmonary hypertension (PPH). Twenty patients with PPH who had undergone diagnostic catheterization in our hospital were studied. The mean follow-up period after the initial catheterization was 6 years, with the longest follow-up being 24.4 years. Seven patients were treated with warfarin as an anticoagulant, combined with either isoproterenol (3 patients) or nifedipine (4 patients) as a vasodilator (AV group). The remaining 13 patients were not treated (control group). Although there were no significant differences in the physical activity or hemodynamics between the groups, improvement was seen in 43% of the AV group and in only 7.6% of the controls. The 5 year survival rate was significantly higher in the AV group (57% vs 15%; P<0.05). Hemodynamics were evaluated repeatedly in 8 patients and improvement was seen only in the AV group. These results suggest that a therapy consisting of a combination of an anticoagulant and a vasodilator may improve the long-term prognosis of PPH.

Effects of a combination therapy of anticoagulant and vasodilator on the long-term prognosis of primary pulmonary hypertension.

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