Natural Way to Cure Asthma

Asthma Free Forever By Jerry Ericson

Finally, international author, asthma expert Jerry Ericson reveals the secrets to overcoming asthma. Asthma Free Forever reveals a proven success methods and simple step-by-step, easy to follow strategies to achieve the success they have been dreaming of. This treatment is based on proven medical research, so users can be sure that it's safe and guaranteed to work. It's also affordable, so they can save money. Asthma sufferers need just apply the info that they will learn from this guide and they can breathe easily without coughing and congestion. They can strengthen their respiratory system and live a healthy and active lifestyle again. With the help of Asthma Free Forever, you can solve your asthma problem for good in just a few days right in the comfort of your own home. This treatment is based on proven medical research, so you can be sure that it's safe and guaranteed to work. Just apply the info that you will learn from this guide and you can breathe easily without coughing and congestion. You can strengthen your respiratory system and live a healthy and active lifestyle again. Read more here...

Asthma Free Forever Summary


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The writer has done a thorough research even about the obscure and minor details related to the subject area. And also facts weren’t just dumped, but presented in an interesting manner.

This ebook does what it says, and you can read all the claims at his official website. I highly recommend getting this book.

Can COPD be distinguished from asthma

COPD is rarely present under the age of 40. Thus, younger patients with wheezing and airflow obstruction are almost always going to have asthma or occasionally one of the less common causes of airway obstruction, such as bronchiolitis. In patients over the age of 40, the overlap between the two con- Table 3.1 A comparison between asthma and COPD. Table 3.1 A comparison between asthma and COPD.

Theophylline Enhanced Elimination

Acute theophylline toxicity Acute charcoal hemoperfusion indications Theophylline level 90 mcg mL at any time. Theophylline level 40 mcg mL when combined with Seizures Hypotension, refractory to fluid loading Ventricular dysrhythmias Protracted vomiting, refractory to antiemetics Chronic theophylline toxicity Monitor theophylline levels every 4-6 hours until

When should bronchodilator therapy be commenced and how often should it be used

The prescriber should begin bronchodilator therapy when patients with COPD report breathlessness or wheeze. Many patients with COPD are unaware of gradual loss of lung function over several decades. It is common for the first symptoms of breathlessness to occur during chest infections. At this stage, the patient may require bronchodilator therapy only during exacerbations but, as the FEV1 declines over a period of years, the patient is likely to require bronchodilator therapy on many or most days. Short-acting bronchodilator drugs are usually prescribed for use 'as required' to relieve breathlessness. Bronchodilators are also used to relieve breathlessness or chest tightness during exercise or they may be used before exercise to increase the patient's exercise capacity or to reduce breathlessness during the planned activity. Bronchodilator drugs may also assist mucus clearance for some patients with COPD (especially in the morning). Mucus clearance is assisted by dilatation of...

Is there a role for oral bronchodilators in COPD

Oral b-agonists such as salbutamol, terbutaline or bambuterol have been shown to have bronchodilator activity in COPD. However, oral b-agonists tend to cause side-effects such as tremor. Inhaled b-agonists can produce equivalent or superior bronchodilation for most patients with less side-effects. Oral theophylline has been shown to have a modest bronchodilator effect in COPD. However, inhaled b-agonists, especially long-acting b-agonists, achieve greater bronchodilation with less risk of toxicity. In patients with severe symptoms, there may be some benefit from the combination of inhaled salmeterol supplemented by oral theophylline (but side-effects were also increased) 11 . It has been suggested that the best way to decide on optimal therapy for COPD patients is to conduct 'n or one' trials where additional drugs such as theophylline are introduced and withdrawn under careful medical scrutiny. However, conventional practice may be just as effective in identifying the subset of...

Are bronchodilators cost effective in COPD

Inhaled bronchodilator therapy is relatively inexpensive. For example, eight puffs of salbutamol per day from a metered dose inhaler costs approximately 70 per annum in the UK. This is clearly cost effective if a patient reports significant benefit. Breath-activated inhalers and dry powder inhalers are more expensive than MDIs. Therefore, for patients who can use an MDI effectively, it is the most cost-effective device. However, for patients who cannot use an MDI after careful instruction, these devices may be cost effective if the patient can use them more effectively. Large volume spacers are a cheap means to enhance the clinical effectiveness of MDI therapy. They are useful and cost-effective for patients with poor inhaler technique. These devices may deliver more aerosol to the lungs than the use of a MDI alone. This is especially useful for patients who require high doses of bronchodilator drugs, thus achieving greater clinical benefit combined with cost-effectiveness. (However,...

Is there a role for nebulized bronchodilators in severe but stable COPD

A small minority of COPD patients may derive additional benefit from the very high dose of bronchodilator therapy that can be delivered from a nebulizer 13,14 . Most patients can derive equal benefit from treatment using hand-held inhalers or spacer devices. Nebulized treatment should only be prescribed after a formal trial comparing the response to nebulized treatment with the response to high-dose treatment using hand-held inhalers as recommended in British Thoracic Society and European Respiratory Society Guidelines for nebulizer use 13,14 .

Are there any chronic sideeffects from bronchodilator therapy

The short-term side-effects of b-agonists are well known (mostly tremor and palpitations). The main side-effect of anticholinergic therapy is a dry mouth. Some patients find that inhaled medication makes them cough. Theo-phylline treatment carries dangers of theophylline toxicity if high doses are given or if the patient is given other drugs which interact with theophyllines. b-Agonists and anticholinergic treatment have been used for decades without any reports of significant cumulative side-effects. Long-acting b-agonists have also been evaluated in COPD without any major concerns about patient safety.

Does theophylline have a role in COPD management

Theophylline has been used for a long time in the management of COPD, but has not been formally studied in large randomized controlled trials 1 . Theophylline is used as a bronchodilator, with doses that give plasma concentrations of 10-20 mg L. At these doses, theophylline results in reduced symptoms and a small improvement in lung function and exercise capacity 2,3 . In one study, theophylline improved dyspnoea by a reduction in hyperinflation, without significant changes in spirometry 4 . This may indicate an effect of the orally administered drug on small-airway function. Whether theophylline improves respiratory muscle function in patients with COPD is controversial, and there is little evidence that respiratory muscle weakness contributes to symptomatology in the chronic stable state. There is increasing evidence that theophylline may have anti-inflammatory or immunomodulatory effects in asthma, and that these may be seen at lower doses than needed for bronchodilatation 5,6...


Asthma is a common condition a careful history and objective recording of simple severity markers, such as pulse and respiratory rate, blood pressure, speech, chest auscultation, mental state, and peak expiratory flow rate, should identify patients who require hospitalization or urgent treatment (Table 4) (12). Detainees with asthma should be allowed to retain bronchodilators for the acute relief of bronchospasm (e.g., salbutamol or the equivalent), with instructions left with the custody sergeant on other treatment if required.

New bronchodilators

Bronchodilators are the mainstay of current management of COPD, and the major recent advances have been in the development of long-acting bron-chodilators. Tiotropium bromide is a very promising new anticholinergic drug that has a very long duration of action. It has a high affinity and dissociates very slowly from M1 and M3-muscarinic receptors in the human lung, and it produces long-term blockade of cholinergic neural bronchoconstriction in human airway smooth muscle. However, its effects on acetylcholine release

Anti Asthmatic

Theophylline, a drug used in the treatment of asthma, has a narrow therapeutic window. Because of this narrow window, it is important to know the serum concentration in order to determine whether it is in the therapeutic or toxic range. Additionally, theophylline and the closely related compound, caffeine, are frequently used to treat apnea in newborns. Like the antiepileptic drugs, these compounds have been analyzed by either MEKC or CZE. MEKC allows direct injection of serum, urine, or saliva in a borate buffer, pH 9.0, in the presence of SDS with separation in about 15 min (73). We obtained a good correlation (r 0.98) to immunoassay when theophylline was measured by CZE in borate buffer, pH 8.5 (15). Zhao et al. (74) determined caffeine and its metabolites by MEKC, and Johansson et al. (75) used CZE to measure theophylline in phosphate-borate buffers. Caffeine, dyphylline, theobromine, and theophylline have also been separated by MEKC in borate buffer, pH 9.3 containing SDS and 30...

Bronchial Asthma

Asthma is an inflammatory disease caused by repeated immediate-phase hypersensitivity and late-phase allergic reactions in the lung leading to the clinicopathologic triad of intermittent and reversible airway obstruction, chronic bronchial inflammation with eosinophils, and bronchial smooth muscle cell hypertrophy and hyperreactivity to bronchoconstrictors (Fig. 19-9). Patients suffer paroxysms of bronchial constriction and increased production of thick mucus, which leads to bronchial obstruction and exacerbates respiratory difficulties. Asthma frequently coexists with bronchitis or emphysema, and the combination of these diseases can cause severe damage to lung tissue. Affected individuals may suffer considerable morbidity, and asthma can be fatal. Asthma affects about 10 million people in the United States, and the frequency of this disease has increased significantly in recent years. The prevalence rate is similar to that in other industrialized countries, but it may be lower in...

Sympathomimetic toxidrome

Features Fight or flight hypertension, tachycardia, sweating, fever, excitation-psychomotor agitation, tremor, seizures, dilated pupils. Causes Amphetamines diet drugs, cocaine, theophylline, caffeine, methylphenidate, mono-amine oxidase inhibitors over-the-counter cold medications, especially those containing phenylpropanolamine (PPA), ephedrine, and pseudoephedrine.

Decontamination Cathartics

Use Most organic and inorganic materials, ASA, acetaminophen, barbiturates, glu-tethamide, phenytoin, theophylline, TCAs. Dose Early (within 1-4 hours) administration of a flavored 8 1 water slurry, 10 1 AC drug, 1-2 g kg body weight (bw). Side effects Vomiting, aspiration, diarrhea, later constipation, possibly small bowel obstruction (SBO) AC is usually combined with a cathartic, particularly 70 sorbitol preferred over Mg citrate.

Other aetiological factors in the pathogenesis of COPD

Asthma A proportion of asthma patients develop an irreversible component that is usually attributed to airway remodelling. It is not known why some asthmatics progress to fixed airflow obstruction but once they have, it is very difficult to differentiate them from patients with COPD on clinical or physiological grounds. Approximately 2 of asthmatics have a forced expiratory volume in 1s (FEVj) below 60 predicted. As asthma is so common, even this small percentage may explain many of those who are labelled as having COPD despite not having any history of exposure to cigarette smoke. In comparison, 10 of moderate smokers (21-40 pack-years) and over 22 of heavy smokers ( 60 pack-years) will develop this severity of airway obstruction 8 .

Inborn Errors of Metabolism

MEKC has been applied to therapeutic drug monitoring. Using MEKC theophylline and its analogues have been separated in plasma. In addition, it has been used to detect and quantitate serum levels of digoxin (44,45). MEKC can also efficiently separate and quantitate antiepileptic drugs that are used in combination, especially ethosuxamide, phenobarbitol, pheny-toin, and carbamazepine (46). (See Chapter 17 for a detailed discussion of the use of CE in therapeutic drug monitoring.) CE has also been used in the clinical and forensic arena (see Chapter 19). In these cases, the use of urine to identify intoxication and or drug abuse of opiates, barbiturates, benzodi-azepines, stimulants, and doping screening is possible within a few minutes (47-51). It is also possible to use CE to screen post mortem fluids for illicit drugs or elevated levels of legal drugs (see Chapter 20). CE has also been applied to determine the tissue concentration of 5-Fluorouracil (5-Fl) in tumor and subcutaneous...

What is the place of the Dutch hypothesis in COPD

A relationship between increased airway reactivity, atopy and the development of COPD was first proposed by Orie et al. in 1961 69 . In other words, smokers with hyperreactive airways could be the susceptible ones who will develop COPD. This hypothesis is still open to debate, as it is not clear whether hyperresponsiveness is the cause or the effect of the decrease in FEV1 in smokers. Airways reactivity and atopy are complex disorders related to a number of genetic and environmental factors leading to allergic inflammation (asthma). This inflammation, however, has recently been shown to be different from that caused by cigarette smoke 70 . In addition, other investigators have suggested that the hyperresponsiveness seen in smokers is the result of abnormal geometry of the airways caused by prolonged smoking, leading to 'reactivity'. In addition, the majority of the studies investigating FEV1 decline have tested airways reactivity at the end of the study (after the initiation of...

Studies in MS and Other Conditions

Chiropractic therapy has been investigated in other conditions. Among neurologic disorders, small or single-case studies note beneficial responses in people with headaches and spinal cord injury. These studies are too small to be conclusive. Chiropractic therapy sometimes is recommended for many other conditions, including asthma, ear infections, and gastrointestinal disorders. No strong evidence supports its use in these conditions.

What is COPD Is it to do with cough and sputum

The productive cough that occurred particularly in smokers and in those working in dusty jobs was shown in the 1950s to be primarily a large-airway problem. Several studies demonstrated an increase in mucosal goblet cells, and the Reid index defined the increased thickness of the mucosa pathologically 1 . The definition of chronic bronchitis used today is that produced by the Medical Research Council (MRC) for epidemiological surveys and not for clinical purposes 2 . The definition restricted chronic bronchitis to 'a productive cough for more than 3 months of the year in each of two successive years'. Thus, chronic bronchitis is related to the productive cough and not to any level of airflow limitation. This symptomatic definition has been used in many epidemiological studies, in which it has been of considerable value, but it is less helpful in managing individuals in clinical practice. For example, patients with bronchiectasis and or with chronic asthma very different pathological...

A new mechanism to lower plasma cholesterol levels in humans the discovery of ezetimibe at Schering

It is of interest to note that combining antihypertensive medicines that lower blood pressure via diverse mechanisms represents a widely accepted regimen. Indeed, a combination of two or more different modes of action are required in some patients to achieve adequate control of blood pressure. The fixed combination ezetimibe simvastatin is another example that shows that combining drugs that approach a medical problem via two different biochemical pharmacologic mechanisms can be beneficial. The concept is not new and is used extensively also in the treatment of cancer, asthma, and congestive heart failure.

Why is it necessary to record spirometry in COPD rather than rely on peak expiratory flow

Adding peak flow measurement to the assessment of asthma control introduced a whole new spectrum of objective assessment to what had been a very subjective exercise. Peak expiratory flow (PEF) is a cheap and simple test and shows a strong correlation with other measures of airflow obstruction. PEF is quick to record, and serial measures also provide an indication of the variability of airflow. It is tempting to extrapolate all the above to COPD. However, the physiology and uses of the measurements are very different in the two conditions. PEF measures the maximum expiratory flow a patient can achieve over a fraction of a second. The level of PEF is related to the airway calibre in asthma, and there is a reasonable correlation of falling PEF with increasing symptoms and vice versa. Asthma is very variable, and the PEF may vary by 200L min between periods of wellness and periods of illness. This may be from 50 of predicted to normal. This is greatly in excess of the variability of the...

Development Of Rituximab For Targeting Cd20 Cells

Rituximab is a chimeric anti-CD20 mAb (Figure 33.1), containing the mouse variable domains of the mAb 2B8 grafted to the human IgG1 constant domains. Rituximab kills CD20+ cells by several mechanisms, including (1) complement-dependent cellular cytotox-icity, (2) antibody-dependent cellular cytotoxicity, and (3) induction of apoptosis.32 Both early phase II testing and phase II pivotal testing of rituximab at 375 mg m2 per week X 4 in relapsed low-grade NHL demonstrated overall response rates of up to 48 (6 CR). The majority of toxic events were infusion related (hypotension, bronchospasm, rhinitis, pruritis, rash, urticaria, and tumor pain) and decreased with repeated dosing. Human antimouse antibodies (HAMA) were not observed. This led to Food and Drug Administration's approval of rituximab for indolent NHL. Its effect against indolent NHL was greatly enhanced by combining the drug with chemotherapy, with 95 overall response rates and 55 CR in patients receiving CHOP...

The Success of Modern Biotechnology

The contribution of biotechnology to medical practice and the pharmaceutical industry can be evaluated by reviewing medical advances and product revenues, as well as looking at pipeline compositions and recent approvals. Biopharmaceuticals are a growing part of research and development pipelines across the pharmaceutical industry, with an ever increasing percentage of discovery stage candidates being described as large molecules. Biologics that have gained regulatory approval over the past 10 years include molecules that offered new approaches to treating a range of diseases, allowing physicians to intervene close to the root cause of the disease rather than alleviating symptoms. Antibodies have been developed for the treatment of infectious disease (Synagis 2004), anemia (Epogen 2005), and allergenic asthma (Xolair 2005), and a number of anticancer antibodies have been added to the options available to oncologists (Walsh 2003a). Additionally,

Contribution to Basic Lung Biology

PGs subserve a number of different biological functions. Versican, because of the high ionic charge of its multiple GAG side chains, plays a critical role in determining the water content or turgor of extracellular matrices. Via this mechanism, versican influences tissue viscoelastic behavior, as well as cell migration and proliferation. Decorin and biglycan are molecules that bind to collagen and affect collagen fibril-logenesis and matrix assembly. They can also act to protect the fibrils from cleavage by collagenases through their coating of collagen fibrils (22). These molecules also bind different growth factors, such as transforming growth factor (TGF)-p and fibroblast growth factor (FGF), and by influencing their bioavailability, modulate their ability to influence cell proliferation and matrix deposition (23,24). PGs have also been shown to influence growth factor receptor expression. For example, HS PG increased platelet-derived growth factor receptor expression on human lung...

Unclassified Adenosine

A naturally occurring nucleoside and G-pro-tein with its own specific adenosine receptors IV boluses of adenosine are indicated to rapidly terminate reentrant and theophylline-induced SVTs. Toxicities Transient asystole, atrial fibrillation, hypotension, bronchospasm. All toxicities are potentiated by the antiplatelet agent, dipyri-damole, an adenosine uptake inhibitor. Higher doses are required for methylxanthine overdoses due to adenosine receptor blockade. Treatment of toxicity Supportive.

Development of QL questionnaires

The daily diary card (DDC) grew out of the idea that, in chemotherapy for lung cancer, it was felt that the main side effects were known but not their duration or the pattern of severity. Thus, the daily diary card was developed based on previous work in other conditions, such as the assessment of night cough in asthma patients and vaginal bleeding patterns. As patients complete the card each evening it was considered imperative to keep the number of questions to a minimum and for practical reasons to use a four or five point categorical scale. In the first MRC trial to use DDCs the consensus opinion was that the questions should address overall QL, a functional measure (physical activity), the main expected side-effect (nausea and vomiting) and two psychological items (mood and anxiety). These questions were changed in subsequent MRC trials depending on the research question.

Synopsis Of The Novel

Camus's The Plague, divided into five parts, chronicles the yearlong story of Oran, a dismal commercial seaport battling the plague. One fine April day in the 1940s Dr. Bernard Rieux, a 35-year-old physician preoccupied with sending his ailing wife to an out-of-town sanitarium, steps on a dead rat. Police magistrate M. Othon notices others. Later, Parisian journalist Raymond Rambert interviews Rieux for a story about lack of sanitation among the Arab population, but because the publication will compromise the truth, Rieux steers him to the dead rat story instead. Rieux's friend, Jean Tarrou, tells him about seeing more convulsing, dying rats. All but the doctor's mother, who comes to keep house for the doctor and his son, are unsettled by the events she has lived through war, depression, and a husband's death. Dead rats begin appearing by the thousands, then just when a sudden drop in the numbers causes the town to feel hopeful, the concierge M. Michel has fever, thirst, delirium, and...

Analytical Applications

Hydrogel nanoparticles have also been employed in a molecularly imprinted polymer (MIP) scheme. The principle behind MIP is based on both shape and molecular-recognition templating. When the polymerization is carried out in the presence of template molecules, it is envisioned that the polymer will rigidify around that template, forming a cavity that is optimized for binding of that molecule. After the templates are removed, it is hoped that the cavity retains that shape and is able to bind and detect that particular molecule or similar molecules in a complex mixture. Ye et al. have synthesized hydrogel nanoparticles in the presence of theophylline and 17 -estradiol. The sensing molecules were dissolved in the mixture of methacrylic acid and trimethylol-propane trimethacrylate and then polymerized either thermally or by UV irradiation. In these studies, they used radioligand binding analysis to determine the sensitivity and selectivity of analyte binding 121 . Competitive binding...

Intestinal mucus secretion and peristalsis

IL-13 works together with IL-4 in producing biologic effects associated with allergic inflammation, discussed in detail in Chapter 19, and in defense against helminths. Some of the actions of IL-13 overlap those of IL-4, and others are distinct. IL-13 functions with IL-4 to induce alternative macrophage activation, which contributes to tissue repair and fibrosis. IL-13 stimulates mucus production by airway epithelial cells, an important component of allergic reactions such as asthma. As mentioned before, both IL-13 and IL-4 can activate B cells to switch to IgE and some IgG isotypes and recruit leukocytes. Unlike IL-4, IL-13 is not involved in TH2 differentiation.

Carvedilol and Heart Failure Banging our Heads against the Textbooks

Likewise, the 'bible' of pharmacology, Goodman and Gilman The Pharmacological Basis of Therapeutics,30 the leading teaching textbook of pharmacology for the biomedical sciences, highlighted special precautions for beta blockers, including the fact that ''heart failure that may develop suddenly or slowly usually in severely compromised heart'' with the use of these drugs. Likewise, Harrison's Principals of Internal Medicine31 lists as adverse effects of beta blockers ''the precipitation of heart failure in patients whom cardiac compensation depends upon enhanced sympathetic drive,'' and in the Textbook of Medicine3 the suggestion is made that ''beta adrenoceptor blockers should not be used in patients with Asthma, COPD chronic obstructive pulmonary disease or congestive heart failure.''

Adenosine Producing Stem Cell Therapy

Adenosine (Figure 4) is an endogenous neuromodulatory agent that has anticonvulsant activity in a variety of animal models.45 Using hippocampal microdialysis probes, adenosine levels were found to be increased 6-31-fold in patients with intractable complex partial epilepsy during seizures,46 suggesting that compounds that mimic adenosine effects, e.g., synthetic adenosine analogs, or facilitate its actions, e.g., adenosine kinase (AK) inhibitors, may be potent and effect AEDs.47 However, as in many other therapeutic areas where modulation of adenosine function has been viewed as a therapeutic option, e.g., neuropathic pain, stroke, asthma, chronic obstructive pulmonary disease (COPD), sleep promotion (see 6.06 Sleep), etc., the efficacy of adenosine and its analogs have been accompanied by unmanageable side effects including sedation and hypotension.48 A novel approach to circumventing the side effects of adenosine has been an 'ex vivo gene therapy' approach, tailoring the local...

What are the criteria of success to justify continuing treatment

There has been much debate as to whether subjective criteria or objective criteria should be used to determine the outcome of a trial of bronchodilator treatment. There is relatively little correlation between symptoms and lung function in individual cases of COPD 3 . It is also possible that some patients may have physiological benefits such as reduced residual volume or reduced gas trapping that may not be detected by simple lung function tests 4 . Therefore, it is reasonable to aim at maximal symptom relief rather than maximum lung function as the main objective of bronchodilator therapy in COPD. Many clinicians find it helpful to monitor FEVi or peak flow improvement during bronchodilator therapy, especially as a large change in FEV1 or PEF may suggest that the diagnosis is asthma rather than COPD. Measurement of exercise capacity such as 6-minute walks, shuttle walks or step tests are helpful in research studies but they are of little value in assessing individual responses to...

Carefully Edible Mushrooms Conclusions

Figure 14.8 Lycoperdon candidum (white puffballs). Common white puffballs (Lycoperdon candidum), release spores when crushed, which can cause acute bronchospasm or lycoperdonosis when inhaled. (Courtesy of Charles P. Sea, M.D., Department of Emergency Medicine, Ochsner Clinic Foundation Hospital, New Orleans, LA. Original Source U.S. Government Document, U.S. Forest Service Document, 1979, Wild Mushrooms of North America. ) Figure 14.8 Lycoperdon candidum (white puffballs). Common white puffballs (Lycoperdon candidum), release spores when crushed, which can cause acute bronchospasm or lycoperdonosis when inhaled. (Courtesy of Charles P. Sea, M.D., Department of Emergency Medicine, Ochsner Clinic Foundation Hospital, New Orleans, LA. Original Source U.S. Government Document, U.S. Forest Service Document, 1979, Wild Mushrooms of North America. )

Airway Hyaluronan General Aspects

Numerous publications in the early 1970s examined the content of hyaluronan in human bronchoalveolar lavage (BAL) from normal and diseased lungs. Increased hyaluronan levels were found in asthmatic and chronic bronchitic patients, as well as in patients suffering from alveolar proteinosis and adult respiratory distress syndromes (13-15). Since hyaluronan is found in the extracellular matrix of the lung parenchyma, many of these studies interpreted an increase of soluble hyaluronan in BAL as a marker of interstitial lung damage

Tissue Kallikrein and Hyaluronan Interaction and Enzyme Inhibition

Tissue kallikrein (TK) is a serine protease that generates lysyl-bradykinin in the airways by cleaving kininogens. Bradykinin is an important mediator of airway inflammation and has been implicated in the pathophysiology of asthma (29,30). Tissue kallikrein is made in submucosal gland cells and secreted into the airway, albeit with inhibited enzymatic activity. The inhibition of TK activity in the airway was a puzzle as it is relatively insensitive, at least in vitro, to known serine protease inhibitors found in the bronchial lumen (31). As TK activity should be suppressed in the airway lumen under normal conditions, it was concluded that enzyme activity was likely regulated by substrate availability. We have now shown, however, that hyaluronan inhibits bronchial TK activity by binding to it (32). Therefore, hyaluronan functions as a natural inhibitor for bronchial TK in the airway lumen. This finding was novel for bronchial TK in the airways, but hyaluronan and other...

Hyaluronan Size and Airway Pathophysiology

In the many airway pathologies, ROS and RNS production is increased and could therefore lead to hyaluronan degradation. Allergen challenge, for instance, causes bronchoconstriction, at least in part, via oxidative stress (62). We, therefore, examined the effects of segmental allergen challenge on the average airway hyaluronan size recovered in BAL from six human volunteers with allergic asthma in comparison with six healthy subjects (samples were kindly provided by Drs Hastie A and Peters S, Thomas Jefferson University, Philadelphia, PA). If our hypothesis that hyaluronan is degraded by oxidative stress applies as in other tissues, the size of recovered hyaluronan should decrease but the amount of soluble hyaluronan should increase due to ROS-mediated cleavage and at least partial release from the cell surface. Figure 1 Changes in hyaluronan size after allergen challenge BAL from asthmatic patients was collected before (a) and 24 h after (b) segmental allergen challenge. The lavages...

Concluding Remarks and Outlook

Forteza R, Abraham J, Hastie A, Peters S, Salathe M, Conner G. Segmental allergen challenge increases hyaluronic acid and tissue kallikrein in bronchoalveolar lavage of asthmatics. Am J Respir Crit Care Med 2000 161 A599. 13. Sahu S, Lynn WS. Hyaluronic acid in the pulmonary secretions of patients with asthma. Biochem J 1978 173 565-568. 17. Vignola AM, Chavez P, Campbell AM, Souques F, Lebel B, Enander I, Bousquet J. Airway inflammation in mild intermitent and persistent asthmatics. Am J Respir Crit Care Med 1998 157 403-409. 31. Christiansen SC, Zuraw BL, Proud D, Cochrane CG. Inhibition of human bronchial kallikrein in asthma. Am Rev Respir Dis 1989 139 1125-1131. 34. Fath MA, Wu X, Hileman RE, Linhardt RJ, Kashem MA, Nelson RM, Wright CD, Abraham WM. Interaction of secretory leukocyte protease inhibitor with heparin inhibits proteases involved in asthma. J Biol Chem 1998 273 13563-13569. Lackie P, Baker J, Gunthert U, Holgate S. Expression of CD44 isoforms is icreased in the...

Is there any point in reversibility testing

Data from the ISOLDE study presented at the 1999 American Thoracic Society meeting did not indicate any predictive value of the response to oral corticosteroids with regard to subsequent benefit from ICS. No other studies have convincingly shown any predictive value from reversibility testing 25 , and in general 'reversibility' is not a discriminatory feature, but rather a characteristic with no obvious cut-off point, varying independently of reversibility, e.g. bronchodilator reversibility 26 .

What dose of inhaled steroids is justified in COPD and with which device

It is obvious from the above that far too few data exist for a satisfactory answer to be given to this important question. In the studies described above, doses were high in comparison with the doses generally used to treat asthma. No dosing studies exist, and it therefore seems reasonable to treat patients with doses similar to those tested in the published trials if treatment with ICS is found to be indicated. Doses should therefore approximate to 1 mg of fluti-casone per day, or equipotent doses of other inhaled corticosteroids. In the two most positive studies 12,15 , the ICS were administered in MDIs using a spacer device. There are comparative studies with dry powder inhalers in asthma, but this is not the case in COPD. If a device other than an MDI plus spacer is used, it therefore seems crucial that a minimum inhalation technique should be taught properly to ensure maximal effectiveness of the device chosen.

What are the risks of longterm inhaled steroid use

In asthma, there is general agreement that the benefits of ICS clearly outweigh the side effects and possible risks associated with long-term use 29 . As this may not be the case in COPD, it is worthwhile to consider both side effects and the potential risks associated with including ICS in the armamentarium of drugs for COPD. Local side effects such as oral candidiasis and hoarseness are quite frequent, and systemic side effects are perhaps not as infrequent as is often believed in asthma. In EUROSCOP, an excess 6 developed bruises on the forearms 5 cm in diameter at least once during the trial 14 , and although it was firmly stated that no other systemic side effects were seen, bruises are markers of systemic effects and it is likely that the study was underpowered to detect more deleterious effects. In a subsample in EUROSCOP, no effects of treatment with ICS were seen on bone mineral density, but as long-term treatment will often be offered to patients with an unfavourable...

Field Amplified Injection in Presence of Salts

Sample injection is 17 of the capillary volume. The compounds iohexol (1), theophylline (2), and phenobarbital (3) were dissolved in (A) the separation buffer (borate 250 mM, pH 8.9, non-stacking), (B) the separation buffer at 25 mM, (C) acetonitrile-water (2 1 v v ), (D) acetonitrile-1 NaCl (2 1 v v ), Adapted with permission from ref. (18). (Note that usually the sample size is kept

Ie Parent Provider or caregiver

Reliance on parental proxy assessments of an adolescent's internal and external functioning is somewhat questionable 4, 54 , as the parents' own anxieties and uncertainties about the future may influence their HRQL reports for their offspring 58 . Studies have consistently shown imperfect concordance rates between self-report and parental proxy ratings for children and adolescents with asthma, cystic fibrosis, chronic headache, limb deficiencies, and cancer 1, 14, 59 . This lack of agreement between proxy and self-

What are the effects of pulmonary rehabilitation on healthcare costs and survival

The costs of caring for patients with COPD are extremely high in comparison with those with asthma, mostly due to the high costs of hospitalization and chronic oxygen therapy in patients with COPD. It is therefore important to look very carefully at all treatments that might reduce the number and duration of hospitalizations. Several uncontrolled trials suggest that pulmonary rehabilitation is effective in decreasing the number of hospital days and number of hospitalizations 70-72 . Hudson et al. followed up 64 patients for 4 years 70 . They showed that for the 44 patients who were alive after 4years, the total number of days of hospitalization decreased from 529 in the year prior to the study to 207 in the last year of the study. Recently, an Italian uncontrolled study also showed a significant reduction in the number of hospitalizations compared to the period before rehabilitation started 38 . However, these positive effects have not yet been confirmed in controlled studies. The...

Background and Principles

To date, most of the literature dealing with transition of care has focused on adolescents and young adults with special healthcare needs 10-16 . According to the United States Maternal-Child Health Bureau, the special needs population has been defined as, those who have or are at increased risk for chronic physical, developmental, behavioral, or emotional conditions, and who also require health and related services of a type or amount beyond that required by children generally 10, 17 . The number of noninstitutionalized children with a chronic condition in the United States alone is estimated to be 4.4 million, or 6.5 of those less than 18 years old 18 . When considering all adolescents with a condition requiring follow-up or surveillance, that figure may be as high as 30 . This population includes those with developmental delay, congenital cardiac anomalies, asthma, cystic fibrosis, diabetes, sickle cell disease, spina bifida, and many with other acquired or congenital disabilities...

The Affected Individual

A second kind of positive effect occurs when an affected individual is given information about his or her genetic makeup, permitting an alteration in lifestyle and life choices that can extend and enhance the quality of life. Chronic obstructive pulmonary diseases such as emphysema, asthma, and bronchitis are the eleventh leading cause of years of potential life lost in the United States. It is fairly well established that genetic factors play an important role in determining age at onset of these diseases and their severity. Individuals who are homozygous for alpha1-antitrypsin deficiency are at greater risk for these lung diseases. That risk is greatly exacerbated by smoking, or by being in an environment with high levels of dust, welding fumes, and a number of other substances. Smoking is regarded as a dominant factor, and contributes as much as 50 percent to the known excess risk, although the interaction of smoking with other factors is not well understood.

Activation of TH2 Cells

Consistent with a central role of TH2 cells in immediate hypersensitivity, larger numbers of allergen-specific IL-4-secreting T cells are found in the blood of atopic individuals than of nonatopic persons. In atopic patients, the allergen-specific T cells also produce more IL-4 per cell than in normal individuals. In animal models, a disease resembling human asthma can be induced by generation of TH2 cells specific for an inhaled antigen or by adoptive transfer of these cells into naive mice. Accumulations of TH2 cells are found at sites of immediate hypersensitivity reactions in the skin and bronchial mucosa.

The Late Phase Reaction

The late-phase reaction may occur without a detectable preceding immediate hypersensitivity reaction. Bronchial asthma is a disease in which there may be repeated bouts of inflammation with accumulations of eosinophils and TH2 cells without the vascular changes that are characteristic of the immediate response. In such disorders, there may be little mast cell activation, and the cytokines that sustain the late-phase reaction may be produced mainly by T cells.

Bronchial constriction

Epinephrine, theophylline FIGURE 19-10 Mediators and treatment of asthma. Mast cell-derived leukotrienes and PAF are thought to be the major mediators of acute bronchoconstriction. Therapy is targeted both at reducing mast cell activation with inhibitors such as cromolyn and at countering mediator actions on bronchial smooth muscle by bronchodilators such as epinephrine and theophylline. These drugs also inhibit mast cell activation. Mast cell-derived cytokines are thought to be the major mediators of sustained airway inflammation, which is an example of a late-phase reaction, and corticosteroid therapy is used to inhibit cytokine synthesis. Cytokines are also produced by Th2 cells (not shown). The pathophysiologic sequence in atopic asthma is probably initiated by mast cell activation in response to allergen binding to IgE as well as by TH2 cells reacting to allergens (Fig. 19-10). The lipid mediators and cyto-kines produced by the mast cells and T cells lead to the recruitment of...

Immunotherapy for Allergic Diseases

In addition to therapy aimed at the consequences of immediate hypersensitivity, mentioned before, clinical immunologists often try to limit the onset of allergic reactions by treatments aimed at reducing the quantity of IgE produced in the patient. Several empirical protocols have been developed to diminish synthesis of allergen-specific IgE. In one approach, called desensitization, small quantities of antigen are repeatedly administered subcu-taneously. As a result of this treatment, specific IgE levels decrease and IgG titers often rise, perhaps further inhibiting IgE production by neutralizing the antigen and by antibody feedback (see Chapter 11). It is possible that desensitization may work by inducing specific T cell tolerance or by changing the predominant phenotype of antigen-specific T cells from TH2 to TH1 however, there is no clear evidence to support any of these hypotheses. The beneficial effects of desensitization may occur in a matter of hours, much earlier than changes...

BAdrenoceptor Antagonists bBlockers

The first -adrenoceptor antagonist, dichloroisoproterenol, was described by I. Slater in 1957. The first clinically useful b-adrenoceptor antagonists, pronethalol and propranolol (Table 2), were discovered and developed by the British pharmacologist Sir James Black. Their usefulness in the treatment of hypertension was first demonstrated in patients by Prichard. Pronethalol was found to be carcinogenic in mice,25 while propranolol was marketed and is still used in the clinic. The discovery of subtypes of b-adrenoceptors, b1 and b2, facilitated the development of additional antagonists with various affinities for the two receptor subtypes. Propranolol is nonselective it has similar affinity for br and b2-adrenoceptors. Blockade of b2-adrenoceptors is likely to cause bronchial constriction, so that propranolol should not be used in patients with bronchial asthma. Propranolol enters the central nervous system and can produce vivid dreams as one of its side effects. Another nonselective...

Should mucolytics be used routinely

Because mucus hypersecretion is a prominent feature of chronic bronchitis, various mucolytic therapies have been used to increase the ease of mucus expectoration, in the belief that this will improve lung function. Stopping smoking is the most effective way to reduce mucus hypersecretion. Anticholinergics may decrease mucus hypersecretion, although most studies have failed to show an effect of inhaled anticholinergics on mucociliary clearance. b2-agonists and theophylline may improve mucus clearance. Steam inhalation (with or without aromatics) may provide symptomatic relief, but there is no evidence that it improves lung function or long-term symptom control.

Recreational Drugs and the Nervous System

Used legally to treat obesity, asthma, and narcolepsy. Herbal products containing ephedra, a drug originally procured from the Mah huang plant and also synthesized in laboratories, have been marketed as treatments for weight loss and for performance enhancement. Methamphetamine is an illegal amphetamine. A crystalline form of methamphetamine called ice is smoked to produce effects similar to crack cocaine.

Drug delivery in COPD

By analogy with asthma, a disease that affects all airways, it has been presumed that the inhaled route of delivery is preferred for the treatment of patients with COPD. However, the disease process in COPD is predominantly in small airways and in the lung parenchyma, which may not be efficiently targeted by the inhalers designed to treat asthma. This may lead to the development of new inhaler devices with particles that have the optimal distribution for peripheral lung delivery. Furthermore, there is a strong argument in favour of oral drug delivery, in order to target lung parenchyma. A further approach is to develop cell-directed therapies. For example, alveolar macrophages appear to play a critical role in COPD and may be targeted by drugs that are designed to be engulfed by these cells, using specially designed liposomes or coated particles of drug. Much more research is needed to optimize drug delivery in COPD patients.

What is the role of antileukotriene drugs in COPD

There are no published studies on the effects of leukotriene receptor antagonists or 5'-lipoxygenase inhibitors in COPD. There is evidence for increased formation of leukotriene B4 (LTB4) in COPD patients 10 , suggesting that inhibition of LTB4 synthesis by a 5'-lipoxygenase inhibitor or blockage of LTB4-receptors on neutrophils by a receptor antagonist may be of potential benefit. Although a 5'-lipoxygenase inhibitor, zileuton, is available for the treatment of asthma in some countries, its effects in COPD have not yet been reported. Several potent LTB4-receptor antagonists have now been developed for clinical use and some are in clinical trial in COPD. Cysteinyl-leukotrienes, as well as causing bronchoconstriction, also induce plasma extravasation and increase mucus secretion. However, the effects of cys-LT antagonists, such as montelukast ands zafirlukast, have not yet been studied in COPD. The major source of these mediators in asthmatic patients are likely to be mast cells and...

Principles And Applications Of Bioregenerative

Structure and function of the pulmonary system pathogenesis, pathology, clinical features, and conventional treatment of pulmonary disorders, including asthma, cystic fibrosis, and pulmonary hypertension and application of regenerative engineering approaches to the treatment of pulmonary disorders.

Neurotoxic Shellfish Poisoning

Larization (opposite of saxitoxin and tetrodo-toxin TTX ). Vectors Clams oysters. Incubation 15 minutes to 3 hours. Symptoms Mild ciguatera-like symptoms with perioral paresthesias and temperature reversal rarely nausea and diarrhea unique conjunctivitis, rhinitis, and or asthmatic bronchitis from aerosolized brevetoxins in breaking surf. Diagnosis By history, TLC or HPLC. Treatment Supportive only. Prognosis Full recovery in 48 hours. Prevention Monitor shellfish bed dinoflagel-late counts adhere to shellfish consumption advisories.

Treatment of Epilepsy in Ayurveda

Similar to traditional Chinese herbal medicine (TCHM), Ayurvedic medicine has been practiced for millennia. The practice includes not only medicinal and dietary treatments but also commonsense behavioral prescriptions such as, Patients with epilepsy should avoid being in places where a seizure could result in injury (1). As with TCHM, many of the compounds used are likely to be pharmacologically active agents. Fortunately, as highlighted in a review by Khan and Balick of the New York Botanical Gardens (2), the effects of many plant species used in Ayurvedic medicine have been preliminarily studied in both humans and animals. Studies now reveal the beneficial effects of several herbal remedies for ailments, including burns (3), diabetes (4), asthma, and pain (5). A study examined the antiepileptic and antianxiety effects of the common Ayurvedic epilepsy herbal medicine Sesbania grandiflora (6). The plant demonstrated clear antiseizure effects when evaluated using the same standard...

Genetic Susceptibility To Immediate Hypersensitivity

The propensity to develop allergies is influenced by the inheritance of several genes. Abnormally high levels of IgE synthesis and associated atopy often run in families. Family studies have shown clear autosomal transmission of atopy, although the full inheritance pattern is multi-genic. Within the same family, the target organ of atopic disease is variable. Thus, hay fever, asthma, and eczema can be present to various degrees in different members of the same kindred. All these individuals, however, will show higher than average plasma IgE levels. Studies of the genetics of allergic diseases in populations have included genome-wide linkage analyses and, more recently, genome-wide association studies. Linkage analyses for atopy asthma susceptibility loci identified several chromosomal regions of importance in allergic disease (Table 19-4). Each of these loci may contain several genes that may contribute to the disease. Some of the genes in these loci may regulate TH2 responses and IgE...

Serum Sample Preparation

Capillary Electrophoresis Drug

For MEKC, if the drug concentration is high enough the serum can be simply diluted in buffer before injection onto the capillary (direct serum analysis), minimizing the matrix effects. This is because the small amounts of serum are solu-bilized by the micelles of the surfactant. Thormann and colleagues (12,13) have successfully applied this technique to the analysis of several drugs such as theophylline, caffeine, and barbiturates by directly injecting serum. Similarly, we applied this technique in the analysis of the new antiepileptic drug felbamate (1) (see Fig. 1). The simplicity, high resolving power, and the small sample size used for the assay render this method suitable for monitoring the levels of these drugs in pediatric patients (Fig. 1).

Cholinergic Toxidrome

SLUDE Muscarinic features Salivation, Lacrimation, Urination, Defecation, Emesis, plus miosis, bronchorrhea and broncho-spasm DUMBBELS Diarrhea, Urination, Miosis, Bronchorrhea, Bronchospasm, Emesis, Lacrimation, and Salivation. Nicotinic features Weakness, fascicula-tions, sweating, tachycardia, hypertension.

Drugs in the Treatment of Allergic Eye Disease

Toms, and topical mast cell stabilisers (sodium cromoglicate, nedocromil sodium and lodox-amide), which are useful in disease prevention if used regularly. The treatment of severe (sight-threatening) disease involves the use of courses of topical and occasionally oral steroids.

When should a second drug be added and does the combination of bagonist and anticholinergic really work better than

There is evidence that combined bronchodilator therapy (b-agonist with anti-cholingeric) produces greater bronchodilation than either drug given alone. This is true whether the agents are given in moderate dose (from hand-held inhalers) or in high doses (from small-volume nebulizers) 5,6 . If the patient needs to use their 'as required' treatment with increasing frequency, they should be advised to try taking the medication on a regular basis (e.g. qid) to see if this diminishes symptoms. If symptoms remain troublesome, the prescriber may increase the bronchodilator dose or consider adding a second agent or a long-acting b2-agonist (see next section).

Immunoglobulins and the Isotype Switch

Stronger antibody production (secondary response in Figure 12.1). This time the IgG antibody producing cells proliferate and release IgG just as quickly as the IgM producing cells. The above pattern of the immune reaction in a normal individual is altered in hypersensitive subjects, mainly by IgE antibodies being produced instead of IgG antibodies. This isotype switch takes place in stimulated B cells in the presence of certain cytokines produced by T helper cells 24 . A normal isotype switch to IgG occurs if the concentration of interleukin-12 (IL-12) is relatively high, whereas a switch to IgE is dependent on the concentration of IL-4. The problem in having high levels of IgE serum is that they bind to mast cells and basophils through the Fc receptor on the cell membrane, thus sensitising these cells. A subsequent exposure to the same allergen induces cross-linking of IgE-bound molecules on sensitised cells. Cross-linking is a term indicating a complex series of events which signal...

Rate of decline in lung function

The US Lung Health Study 39 observed 4000 patients with mild COPD over 5 years with and without an anticholinergic bronchodilator. While the drug had no effect on rate of loss of FEV1, the authors did note as a secondary end point that the rate of loss of FEV1 was significantly less in those who quit smoking compared to those who continued. They also observed that those with bronchial hyperreactivity had an increased rate of loss compared to those without. Thus, both exogenous and endogenous factors may affect the rate of decline. As a generalization, the average fall in FEV1 in susceptible smokers seems to be in the order of 60 mL per year (i.e. twice that of non-smokers) 40 .

Allergic Conjunctivitis

Unfortunately, patients with asthma and eczema can experience recurrent itching and irritation of the conjunctiva. Although atopic conjunctivitis tends to improve over a period of many years, it might result in repeated discomfort and anxiety for the patient, especially as the cornea can become involved, showing a superficial punctate keratitis or, in the worst cases, ulcer formation and scarring.

Ocular Surface Diseases

Allergic conjunctivitis and perennial conjunctivitis are fairly acute ocular surface disorders. However, vernal conjunctivitis, atopic keratonjunctivitis, and giant papillary conjunctivitis are chronic disorders.93 The hallmarks of allergic conjunctivitis are itching, redness, swelling, tearing, and temporary acute photophobia caused by various mast cell mediators released from mast cells when an allergen contacts the conjunctiva. The acute allergic conjunctivitis may develop into a chronic disease if left untreated, and this causes corneal and conjunctival remodeling and ulceration, sometimes accompanied by bacterial infection. Since mast-cell-derived histamine is the major culprit in allergic conjunctivitis, topical ocular antihistamines, such as emedastine, levocabastine, azelastine, and ketotifen, were considered the drugs of choice, often supplemented with vasconstrictors (e.g., oxymetazoline) and edema reducers (nonsteroidal anti-inflammatory agents and corticosteroids)....

Is the choice of inhaler device important

Ence between the bronchodilator response achieved by different devices. The most important factor is to choose a device that the patient is able to use. For many COPD patients (especially the elderly), a breath-activated MDI or an MDI with spacer may be the easiest device for the patient to use. A recent meta-analysis of trials of bronchodilator therapy using different hand-held inhaler devices showed that here was no important difference in clinical outcomes between metered dose inhalers, breath-activated inhalers or dry powder devices 12 . This meta-analysis involved patients with asthma but it is likely that these findings would apply equally to COPD patients (provided they can use the device which is prescribed for them). Most bronchodilator studies with spacer devices have used large (750 mL) spacer devices such as the Volumatic or Nebuhaler device. However, these devices are rather large and many patients prefer a smaller device such as 'Aerochamber' although its use has not...

Outline Of Therapies Available In The Drug Delivery Field

Drug delivery systems can take the form of microspheres,131718 nanospheres,19-22 hydrogels,23-25 capsules,26-28 transdermal membranes,23 29 and liposomes.47 30-33 Their use ranges from the release of growth hormones, anti-inflammatory agents, anticancer agents, and antibiotics, to gene therapy, diabetes, delivery of contraceptives, and respiratory sickness such as asthma,1 434-37 as well as many others. In this chapter, we will focus mainly on injectable or implantable drug delivery systems, such as micro- and nanoparticles and scaffolds that can present a dual function to support tissue regeneration and to enhance it by itself or by loaded therapeutic agents. The tissue engineering applications of scaffolds as carriers for delivering bone and cartilage active agents will be covered later in this chapter.

Asian Proprietary Medicine or Asian Patent Medicine

Several studies of the chemical composition of these preparations have found that they frequently contain potentially toxic ingredients. Recent data indicate that approximately one-third of these products contain drugs or dangerous metals. Drugs that have been found include diazepam (Valium), steroids, and prescription asthma medications. Toxic metals sometimes found in these products are arsenic, mercury, lead, and cadmium.

Epidemiology of Reproductive Toxicology

Antimicrobials, antiemetics, theophylline, caffeine, ethanol, and nicotine. From 15 to 25 of pregnant women report licit drug use (ethanol nicotine), or illicit drug use (marijuana cocaine heroin), or have positive urine drug screens during pregnancy. Analgesics, vitamins, iron, antibiotics, theoph-ylline, and psychotropic medications account for 50 to 80 of all reported toxic ingestions by pregnant women.

Shalender Bhasin md Atam B Singh md and Robert Christiansen md

He had had mild bronchial asthma for 3 yr his asthma was controlled with intermittent use of a metered-dose inhaler. His medications included prednisone 5 mg twice daily, 9-a fludrocortisone 0.2 mg daily, albuterol inhaler as required for bronchial asthma, sustained release theophylline 300 mg daily, and testosterone enanthate 200 mg intramuscularly every 2 wk. At the time of his clinic visit, he had not received his testosterone injections for several months.

Physiologic Environment

This procedure of oxygen enrichment should not be done without proper instruction. Parents are taught the oxygen enrichment program only after they attend the What to do about your brain-injured child (WTD) course and their child has been evaluated at The Institutes. Alternatively, parents can attend the WTD course and the information can be given to the child's primary doctor, to start the oxygen enrichment program. Oxygen enrichment is not appropriate for some children with cardiac defects. It should not be used in children with respiratory diseases in which carbon dioxide is abnormally retained, such as uncontrolled asthma or obstructive pulmonary disease. Rebreathing should never be done when there is pneumonia, fever, vomiting, or severe upper respiratory infections.

Introduction Analysis Of Urinary Drugs In Clinical And Forensic Toxicology

Clinical and forensic toxicology is concerned with the detection, identification, and measurement of toxic compounds and their metabolites in human body fluids and tissues. Most often the toxic compounds are drugs taken either accidentally or intentionally in quantities sufficient to cause an adverse reaction or death. Analysis and identification of a possible drug or drug combinations, toxicological drug screening and confirmation should encompass as many different classes of drugs as possible. The most important classes being salicylate, paracetamol, antiepileptics, antidepressants, neuroleptics, hypnotics (benzodiazepines, barbiturates, diphenhydramine), digoxin, and theophylline, as well as many illicit drugs, such as opiates, methadone, D-lysergic acid diethylamide (LSD), cocaine, and or its major metabolite benzoylecgonine, cannabinoids and amphetamines. Currently, urinary drug monitoring has established itself as the basis of clinical and forensic toxicology. It is also the...

Druginduced myocardial damage

Several drugs of abuse have been associated with increases in cardiac troponin without evidence of ischemia. These include alcohol when heavily consumed (75), cocaine (76, 77), and amphetamines (7). Small clinical studies and case reports have documented increased cardiac troponin concentrations following CO exposure, theophylline overdose, snake bites, and during treatment with fluvastatin (7,78). Two case reports also documented an apparent propofol-induced cardiac and a skeletal muscle rhabdomyolysis both cases resulting in fatality (79).

Medical Complications Direct Results of Cocaine

In terms of pulmonary effects, pneumomediastinum and cervical emphysema have been reported after smoking cocaine due to alveolar rupture with prolonged deep inspiration and Valsalva's maneuver (Aroesty, Stanley, & Crockett, 1986). Other respiratory complications of inhaling or smoking freebase cocaine include abnormal reductions in carbon monoxide diffusing capacity (Itkonen, Schnoll, & Glassroth, 1984), granulomatous pneumonitis (Cooper, Bai, Heyderman, &Lorrin, 1983), pulmonary edema (Allred &Ewer, 1981), thermal airway injury, pulmonary hemorrhage, hypersensitivity reactions, interstitial lung disease, obliterative bronchiolitis, asthma, and persistent gas-exchange abnormalities (Laposata & Mayo, 1993). Respiratory manifestations include shortness of breath, cough, wheezing, hemoptysis, and chest pains. Severe respiratory difficulties have been reported in neonates of abusing mothers. Inhalation of hot cocaine vapors may also result in bilateral loss of eyebrows and eyelashes...

Major Depressive Disorder

Elimination half-life of approximately 6 weeks when considered with its potent metabolite norfluoxetine. Sertraline, citalopram, and escitalopram have few potential drug-drug interactions, but all can have gastrointestinal side effects including nausea, vomiting, and diarrhea, as well as sleep alterations, weight changes, sexual dysfunction, and extrapyramidal effects such as a high-frequency, low-amplitude tremor. The tricyclics produce significant anticholinergic effects and may induce delirium, cognitive slowing, urinary retention, dry mouth, and orthostasis these are not recommended for routine use in this vulnerable population. Similarly, monoamine oxidase inhibitors are not recommended for patients with HIV and AIDS. This class of medications poses an extraordinary risk, since persons with HIV and AIDS are often on complex and frequently changing drug regimens and also have the concurrent risk of hypertensive crisis if exposed to certain foods or other medications. These include...

Sleep Disturbance In

Methylphenidate and other psychostimulants used to treat apathy and fatigue in HIV-infected patients can cause insomnia, although restriction of dosing schedules to the earlier part of the day should avoid this side effect. Insomnia and non-restful sleep have been-reported early in treatment with efavirenz and may also cause more chronic sleep difficulty. Studies have found longer sleep latency and shorter duration of deep sleep in patients treated with efavirenz compared with controls as well as higher efavirenz plasma levels in patients with insomnia and or reduced sleep efficiency than in those being treated with efavirenz who did not have sleep complaints (Gallego et al., 2004). In addition, efavirenz has been associated with vivid dreams and nightmares (American Psychiatric Association, 2000) that may result in disturbed and less restful sleep. Abacavir, stavudine, didanosine, and zi-dovudine (AZT) have also been linked to insomnia, with placebo-controlled studies showing more...

Mucosal Immunity in the Respiratory System

Protective humoral immunity in the airways is dominated by secretory IgA, as in other mucosal tissues, although the amount of IgA secreted is much less than in the gastrointestinal tract. Secretory IgG plays an important role in the upper airway. The anatomic sites of naive B cell activation, differentiation, and IgA isotype class switching may vary but include tonsils and adenoids in the nasopharynx and lymph nodes in the mediastinum and adjacent to bronchi in the lungs. There are relatively few aggregated or isolated lymphoid follicles in the lamina propria in the lower airways compared with the gut and likely less initiation of humoral immune responses in these locations. The homing of IgA-secreting plasma cells back into the airway tissue in proximity to respiratory mucosal epithelium depends on the chemokine CCL28 secreted by respiratory epithelium and its receptor CCR10 on the plasma cells. IgA and IgG are transported into the airway lumen by the same poly-Ig receptor and FcRn...

The Nature of Allergens

The natural history of antigen exposure is an important determinant of the amount of specific IgE antibodies produced. Repeat exposure to a particular antigen is necessary for development of an allergic reaction to that antigen because switching to the IgE isotype and sensiti-zation of mast cells with IgE must happen before a hyper-sensitivity reaction to an antigen can occur. Individuals with allergic rhinitis or asthma often benefit from a geographic change of residence with a change in indigenous plant pollens, although environmental antigens in the new residence may trigger an eventual return of the symptoms. A dramatic example of the importance of repeated exposure to antigen in allergic disease is seen in cases of bee stings. The proteins in the insect venoms are not usually of concern on the first encounter because an atopic individual has no preexisting specific IgE antibodies. However, an IgE response may occur after a single encounter with antigen, and a second sting by an...

Infections Transmitted Through the Respiratory Route

Respiratory tract infections are common, usually mild, and self-limiting, although they may require symptomatic treatment with paracetamol or a nonsteroidal antiinflammatory. These include the common cold (80 rhi-noviruses and 20 coronaviruses), adenoviruses, influenza, parainfluenza, and, during the summer and early autumn, enteroviruses. Special attention should be given to detainees with asthma or the who are immunocompromised, because infection in these people may be more serious particularly if the lower respiratory tract is involved.

Differential Diagnosis Drug Induced Bradycardia

Angina Reduce anginal attacks and decrease post-myocardial infarction mortality. Tachydysrhythmias Used in theophylline overdose, butadenosine preferred over P-blockers. Tremor Propanolol over prescribed agitation, stage fright, and panic attacks ( shakes ). Migraine headaches. Bronchospasm Nonselectives prevent bron-chodilation and promote bronchospasm in chronic obstructive pulmonary disease (COPD) patients.

Allergic Diseases In Humans Pathogenesis And Therapy

Mast cell degranulation is a central component of all allergic diseases, and the clinical and pathologic manifestations of the diseases depend on the tissues in which the mast cell mediators have effects as well as the chronicity of the resulting inflammatory process. Atopic individuals may have one or more manifestations of allergic disease. The most common forms of these diseases are allergic rhinitis (hay fever), bronchial asthma, atopic dermatitis (eczema), and food allergies. The clinical and pathologic features of allergic reactions vary with the anatomic site of the reaction, for several reasons. The point of contact with the allergen determines the organs or tissues that are involved. For example, inhaled antigens cause rhinitis or asthma, ingested antigens often cause vomiting and diarrhea, and injected antigens cause systemic effects on the circulation. The concentration of mast cells in various target organs influences the severity of responses. Mast cells are particularly...

Innate Immune Cells

NKT cells produce both T helper 1 (Th1) and T helper 2 (Th2) cytokines, depending on their mode of activation, underscoring key regulatory roles for the cytokine milieu and glycolipid antigen repertoire present in the tumor microenvironment. Indeed, NKT cells can undermine tumor rejection in some tumor models through a mechanism that involves transforming growth factor P (TGF-P) production by Gr-1+ myeloid suppressor cells (Terabe et al., 2003). Studies have indicated that the CD4- NKT cells effectuate tumor rejection in the MCA-induced fibrosarcoma and B16F10 melanoma models, whereas CD4 + NKT cells contribute to the pathogenesis of inflammatory diseases (e.g., asthma) by the secretion of IL-4, IL-5, and IL-13 (Akbari et al, 2006 Crowe et al, 2005). A deeper understanding of the factors determining the induction of NKT cell subsets during tumor development is an important goal of further investigation.

Scombroid Fish Poisoning

Symptoms Sudden warm facial flushing and sunburn-like rash, metallic-peppery taste, perioral burning and blistering sensations then urticaria, pruritus, bronchospasm, palpitations, tachycardia, hypotension fewer gastrointestinal symptoms of abdominal cramps, nausea, vomiting, and diarrhea. gas chromatography mass spectrometry, high serum and urine histamine and saurine levels. Treatment Severe poisoning gastric emptying, then AC gut decontamination otherwise, Hj-and H2-blockers, P-agonists for bronchospasm with wheezing, and consider corticosteroids for allergic bronchospasm and urticaria pruritus. Prognosis Symptoms resolve in 12-24 hours even without treatment.

Mechanism and Toxicity

Toxicity Gastrointestinal (nausea, vomiting, diarrhea) allergic manifestations CNS Allergy 5 manifest penicillin sensitivities local pruritus, asthma 1 develop ana-phylaxis. Treatment O2, epinepherine-nor-epinepherine, P2-agonists, steroids, H1- and H2-blockers, theophylline, fluids. Consider glucagon for severe hypotension. CNS Seizures due to inhibition of GABA-to-receptor binding. Treatment benzodi-azapines barbiturates.

Herbs Containing Caffeine

Caffeine is perhaps the most commonly used stimulant in the world. Several plants produce caffeine and theophylline and theobromine, which are close relatives of caffeine. Most people readily know that coffee (Coffea arabica and C. robusta) and tea (Camellia sinensis) have caffeine in them, but several other herbal medicines also contain caffeine. Cocoa (Theobroma cacao) is the main ingredient in chocolate-flavored foods, from candy bars to hot cocoa. There are usually 20 to 60 milligrams of caffeine in an average chocolate bar (200 grams of chocolate). That isn't a lot of caffeine, but eating several pieces of chocolate, particularly dark chocolate, can add up to a significant amount. It also takes the body several hours to process caffeine, so eating several pieces throughout a day can have a cumulative effect. Cocoa also has higher amounts of theobromine in it, which acts in a manner similar to caffeine.

Role of longacting bagnoistsdo they act mainly on quality of life rather than on lung function variables

There is increasing evidence that long-acting b2-agonist treatment is effective for patients with COPD. This treatment has been shown to increase FEV1 and peak flow, improve symptom control and improve quality of life compared with 'prn' use of short-acting b-agonist therapy 7,8 . Treatment with a long-acting b-agonist bronchodilator is likely to be of greatest benefit if prescribed for patients with persistent symptoms despite the use of short-acting b-agonists on a 'prn' basis. Some trials have shown a reduction in exacerbation rates or delay in the time to first exacerbation during treatment with long-acting b2-agonists 9 . If a patient with COPD is prescribed a long-acting b-agonist, they should continue to use their short-acting bronchodilator inhaler on a 'prn' basis for episodes of breathlessness. There is some evidence that combined treatment with salmeterol and anticholinergic treatment (ipratropium bromide) or with oral theophylline treatment is more effective than treatment...

Differential Diagnosis

Mood and anxiety disorders, learning disorders, mental retardation, pervasive developmental disorders, organic mental disorders, and psychotic disorders may all present with impairment of attention, as well as hyperactive impulsive behaviors. The diagnosis of ADHD in DSM-IV-TR requires that the symptoms of inattention cognitive disorganization and impulsivity hyperactivity are not better accounted for by one of the above conditions. Differentiating ADHD from bipolar disorder in childhood is complicated by the low base rate of bipolar disorder and the variability in clinical presentation. Even though there are phenomenological similarities between the two disorders, there is little evidence to suggest that most children with externalizing symptoms are at risk for bipolar disorder. A positive family history of bipolar disorder is especially helpful in diagnosing bipolar disorder in children. In addition, a variety of medical conditions such as epilepsy, Tourette's disorder, thyroid...

Cell Death

Benjamin Weiss Airway Wall Remodelling in Asthma, 1996, A.G. Stewart Drug Delivery Systems, 1996, Vasant V. Ranade and Mannfred A. Hollinger Brain Mechanisms and Psychotropic Drugs, 1996, Andrius Baskys and Gary Remington Receptor Dynamics in Neural Development, 1996, Christopher A. Shaw Ryanodine Receptors, 1996, Vincenzo Sorrentino Inflammatory Cells and Mediators in Bronchial Asthma, 1990, Devendra K. Agrawal and Robert G. Townley

G13 Case

A major lesson came belatedly from the clinical trials and toxicological studies of the beta agonists. Soterenol, the bioisostere of isoproterenol, had almost completed phase III clinical trials as a bronchodilator for asthmatics, and me-suprine was in phase III for peripheral vascular disease and premature labor as a uterine relaxant when preliminary results from chronic toxicity and carcinogenicity studies became available. At necropsy 20 of 50 rats in the high dose group had benign tumors, mesovarial leiomyomas, which appeared like a third ovary. No tumors were found after 18 months, only after 24 months. With a heightened concern for tumors and carcinogenicity at the Food and Drug Administration (FDA) in the 1960s, all clinical trials were stopped and all patients who had received drug were to be followed for their lifetime. The FDA even assumed the MeSO2NH group was responsible for the leiomyomas, although the rats were dosed with 10 000 times the amount of compound that would...


T lymphocytes are increased in lung parenchyma, and in both peripheral and central airways in COPD 28,29 . In contrast to asthma, in which the CD4 cell is prominent in the airway, CD8+ cells are increased in the airway mucosa in COPD patients and may cause cytolysis and apoptosis of alveolar epithelial cells 29,30 . Although there is an association between T lymphocytes and the amount of alveolar destruction and airflow limitation 28,31 the role of T cells in the pathogenesis of COPD is not yet certain. Although eosinophils play an important part in the mechanisms of airway inflammation in asthma, their role in COPD is obscure. There are conflicting reports concerning their numbers in stable disease, but most reports have


G., Berry, G. J., Wahlstrom, J., Kronenberg, M., DeKruyff, R. H., and Umetsu, D. T. (2006). CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N. Engl. J. Med. 354, 1117-1129. Boon, T., and van der Bruggen, P. (1996). Human tumor antigens recognized by T lymphocytes. J. Exp. Med. 183, 725-729. Brandes, M., Willimann, K., and Moser, B. (2005). Professional antigen-presentation function by human gammadelta T Cells. Science 309, 264-268.

Yoga and Epilepsy

For several decades, the physiologic and neurophysiologic effects of relaxation and meditation have been studied. Studies document physiologic changes in the muscu-loskeletal, respiratory, metabolic, and cardiovascular systems during yoga (20). These effects benefit patients with high blood pressure (21), asthma (22), and carpal tunnel syndrome (23). Additionally, yoga has measurable effects on the brain. Several studies document increased alpha waves in the EEGs of subjects performing yogic breathing and meditation (24). Alpha waves are brain waves that are abundant during calm, quiet, wakefulness. Positron emission tomography (PET) scans (studies that analyze brain blood flow and oxygen consumption) also show changes in cerebral blood flow during meditation (25). These effects on the brain may explain yoga's positive influence on stress management.


Timolol and other beta-blockers are effective over a 12-h period and need to be instilled only twice daily. As an ocular hypotensive agent, these are probably not quite as effective as pilo-carpine,but many cases of chronic glaucoma are now satisfactorily controlled by them and furthermore, the drug may be used in combination with pilocarpine. Beta-blockers have the further advantage that they do not cause any miosis. The main side effects of beta-blockers are bronchospasm, reduced cardiac contractility and bradycardia. They are, therefore, contraindicated in patients with chronic obstructive airway disease, heart block, hypotension and bradycardia.

Martin Connolly

Respiratory disease is the second commonest cause of disability in old age 1 , and chronic obstructive pulmonary disease (COPD) in turn is the commonest disabling respiratory condition in this age group. Estimates of the overall prevalence of COPD in the elderly population vary widely, from around 16 to nearly 30 2-6 . These differences are likely to be largely dependent on differences in smoking prevalence, pollution levels, and poverty levels between subpopulations examined. Most epidemiological surveys, however, agree on the point that a large proportion of chronic obstructive pulmonary disease in old age remains undetected and untreated. A further complicating factor in epidemiological assessment is the accuracy of diagnostic labelling. Many elderly patients with chronic asthma and limited treatment responsiveness could equally well be (and often interchangeably are) labelled as either asthmatics or COPD sufferers. For the purpose of this chapter, chronic poorly responsive asthma...

Ronan ODriscoll

Why use a bronchodilator in stable COPD Bronchodilator treatment provides symptomatic relief for patients with COPD. The main indication for the use of bronchodilator drugs is the relief of breathlessness or wheeze. For many patients with mild COPD, bronchodilator therapy (to be used as required) might be their only requirement. Bronchodilator medication has no effect on prognosis in COPD 1 . Therefore, there is no need to insist on regular medication. The patient can be advised to take their bronchodilator therapy as required. Patients with troublesome symptoms are likely to use a short-acting bronchodilator several times per day. Many such patients may benefit from the introduction of a long-acting b-agonist bronchodilator. For patients with more advanced COPD, bronchodilator therapy should be used as an adjunct to other therapy such as oxygen (if hypoxic), pulmonary rehabilitation (if disabled by breathlessness) and smoking cessation (if still smoking). It is important to emphasize...

J0rgen Vestbo

It will come as no surprise to practicing clinicians that inhaled corticosteroids (ICS) are widely used in the management of chronic obstructive pulmonary disease (COPD). It is the general impression that as many COPD patients as asthma patients are treated with ICS treatment often includes high-dose ICS, is continued for years without much thought of monitoring the effect, and little is done to evaluate potential systemic side effects. The widespread use of ICS was recently documented in a Canadian survey 1 , in which 43 of hospitalized patients using ICS were suffering from COPD and not asthma, which is the registered indication in Canada as well as in most other countries. There are no good studies on why inhaled corticosteroids became so popular in COPD in spite of their lack of official recognition and at a time when few data on long-term effects were available. It is my belief that they were used for several reasons many doctors believed that COPD differed very little from...

What else do we know

If we look at studies using other outcomes than long-term change in lung function and exacerbations, a somewhat mixed picture emerges, and it is not obvious whether it helps us to clarify the position of ICS. Several short-term studies have been published looking at the effect of ICS on various surrogate markers, supposedly reflecting ongoing inflammation. Importantly, studies of cell types and mediators from bronchoalveolar lavage fluid have shown clear differences between asthma and COPD 21,22 , and the choice of inflammatory markers is therefore crucial. It would be outside the scope of this chapter to summarize findings in this area some studies have been interpreted as showing an effect of ICS on relevant measures, whereas others have been interpreted as negative.

Passive Smoking

Inhalation of smoke in an enclosed space, especially for prolonged periods of time, is not healthy. It may trigger an asthmatic attack in a child, for example. There are studies that show if nonsmokers are in a 10 x 10 square foot room with smokers, within a short time of exposure, effects on the cardiovascular system, e.g., heart rate and blood pressure, can be observed. This is not surprising. Nicotine, after all, is a drug that can cause cardiovascular and central nervous system effects. The data for passive smoking causing lung cancer, however, are skimpy at

Case Example

She told herself that she could have prevented her mother's death if she had only taken her to a different doctor. At the same time, she also felt that she was wrong to be so devastated by the death. She thought that her sisters and friend were right. She should be over it by now. She began to wonder if others would be better off without her and stopped using her asthma medication. She occasionally ran a red light when driving something very uncharacteristic for her. Although she was seriously angry with God, she had always been a religious person and she feared that taking her own life might mean that she would never see her mother again.

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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