signs of asthma: Respiratory

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Tuesday, September 24, 2013

Most Common Diseases of Age 50+: Asthma (Respiratory Disease) - The Causes

Respiratory Disease is defined as medical conditions which affect the breathing organ and tissues including Inflammatory lung disease, Obstructive lung diseases,Â Restrictive lung diseases, Respiratory tract infections, trachea, bronchi, bronchioles, alveoli, the nerves andÂ muscles breathing , etc,.
I. AsthmaÂ
Â Asthma is a chronic inflammatory disease affecting the air way of the lung with recurring symptoms, such as wheezing, chest tightness, shortness of breath, and coughing. The disease affects people of all ages, and mostly starts during childhood. In the study of 463,801 children aged 13-14 years in 155 collaborating centres in 56 countries. Children self-reported, through one-page questionnaires, symptoms of these three atopic disorders. In 99 centres in 42 countries, a video asthma questionnaire was also used for 304,796 children, found that for asthma symptoms, the highest 12-month prevalences were from centres in the UK, Australia, New Zealand, and Republic of Ireland, followed by most centres in North, Central, and South America; the lowest prevalences were from centres in several Eastern European countries, Indonesia, Greece, China, Taiwan, Uzbekistan, India, and Ethiopia(1). In the United States, approximately, asthma affects 25 million people, 7Â million of them are children.

B.1. Causes
1. Smoking and second hand smoke
Smoking is considered as one of major cause of lung diseases, including asthma. According to the study by Texas Tech University Health Science Center, Airway mucosal permeability is increased in smokers, which could lead to increased clearance of inhaled corticosteroids from the airways. Smokers also have decreased histone deacetylase activity, which is necessary for corticosteroids to fully suppress cytokine production, and can lead to corticosteroid resistance. The study also indicated that In asthmatic patients who smoke, disease control is poorer than in asthmatic nonsmokers. Of all forms of SHS, maternal exposure seems to have the largest impact on asthma by increasing the frequency and severity of the disease and decreasing lung function. Asthmatic children exposed to multiple household smokers face an increased risk for respiratory illness-related absences from school, and these effects persist during adolescence but weaken during adulthood(6).

2. Allergies
People who are sufferred from alergies are most likely to develop asthma. The allergic march is a progression of atopic disease from eczema to asthma, and then to allergic rhinoconjunctivitis. It appears to be caused by a regional allergic response with breakdown of the local epithelial barrier that initiates systemic allergic inflammation. Genetic and environmental factors predispose to developing the allergic march, according to the study by Department of Surgery, Cape Cod Hospital, Hyannis(7). Other indicated that Allergen exposure contributes to the risk of asthma exacerbations, but other precipitating factors, such as viruses, can interact and increase the risk. According to the study by hÃ´pitaux universitaires de Strasbourg, deteriorating asthma can be related to increased exposure to allergens, particularly allergens from house dust mite, cockroach, cat, rodent, mold or pollen. Several studies have demonstrated that sensitization to respiratory allergens and allergen exposure increases the risk of exacerbation of asthma. When asthma exacerbations are work-related, occupational allergens may be implicated(8).

3. Occupational and environmental exposures
Occupational and exposure history may increase the risk of respiratory problems. According to a report by Dr, Hoy RF., there is a case of a man, 23 years of age and previously well, presents with 2 months of cough, shortness of breath and weight loss. Occupational and exposure history identifies him as commencing work at a mushroom farm 12 months ago where he is exposed to dust from the mixing of mushroom compost. He is not required to use respiratory protection at work. His cough and chest tightness usually start in the afternoon at work and persist into the evening. Some of the effects of exposures may be immediate, whereas others such as asbestos-related lung disease may not present for many decades. Airborne contaminants may be the primary cause of respiratory disease or can exacerbate pre-existing respiratory conditions such as asthma and chronic obstructive pulmonary disease(9).

4. Obesity
Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese. In the study to to examine the relationship between central obesity and asthma outcomes in a group of Iranian asthma patients, researchers showed that there is a significant association of WHR-based central obesity with forced expiratory volume in 1 s (FEV(1)) (Î² = -9.04; p-value = .044) and forced vital capacity (FVC) (Î² = -10.52; p-value = .012). Logistic regression analysis showed a significant increased risk of asthma attacks in 3 months with Asian WC-based central obesity [odds ratio (OR) = 6.31, 95% confidence interval (CI): 1.16-34.41]; emergency room (ER) visits with NIH WC-based (OR = 5.15, 95% CI: 1.36-19.55) and Asian WC-based (OR = 18.72, 95% CI: 1.92-182.63) central obesity; and hospitalization in 1 year with NIH WC-based (OR = 5.28, 95% CI: 1.28-21.84) and Asian WC-based (OR = 12.39, 95% CI: 1.29-119.53) central obesity(10).
Some study suggested that asthma in the obese patient might be more responsive to leukotriene modifiers, orchestrated by leptin and/or adiponectin derived from adipose tissue, than to inhaled corticosteroids, possibly reflecting differences in the underlying airway inflammation in obese vs. non-obese asthmatics(11).

5. Exercise-Induced Asthma
Vigorous exerciseÂ can cause a narrowing of the airways inÂ Â asthma patient.There is a report ofÂ a 44-year-old man with a history of seasonal allergic rhinitis but no asthma, who reported difficulty breathing when playing tennis andÂ a 45-year-old woman who presented with persistent, generally well-controlled asthma, who was now experiencing bouts of coughing and wheezing during exercise. EIB is a frequently encountered problem among patients presenting to primary care specialists. Affected patients should be made aware of the importance of proactive treatment with a short-acting beta agonist before initiating any exercise(12).

6. Gastroesophageal reflux disease (GERD)
Gastroesophageal reflux disease (GERD), also known as gastro-oesophageal reflux disease (GORD), gastric reflux disease, or acid reflux disease, is defined as a chronic condition of liquid stomach acid refluxing back up from the stomach into the esophagus, causing heartburn. According to the study of “Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.” by DeVault KR, Castell DO; American College of Gastroenterology, GERD is defined as symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. It is considered as one the causes of asthma. There is a report ofÂ an 11-year-old boy who was referred to a pediatric respiratory clinic for asthma that was not responsive to inhaled medications. The child presented with a one-year history of dyspnea on exertion, cough and wheeze. He also complained of chronic dyspepsia. The presence of GI symptoms, in addition to abnormalities on chest radiograph and spirometry, suggested the presence of achalasia(13).

7.Â Sinusitis
Sinusitis is defined as a condition of inflammation of the paranasal sinuses of which can develop headache as a result of exposure to a cold or flu virus, or an allergic reaction to pollen, mold, dust or smoke, etc..Sinusitis affects 37 million people each year. Some researchersÂ suggested that there is a close relationship between allergic rhinitis and asthma, food allergy, and atopic dermatitis. Rhinitis and sinusitis often coexist and are commonly referred to with the term rhinosinusitis. These conditions are also linked in the so-called atopic march, which is the sequential appearance of atopic manifestations starting with atopic dermatitis and later followed by food allergy, allergic rhinitis, and asthma(14).

8.Â Upper Respiratory Infections
upper respiratory viral infections are strongly associated in time with hospital admissions for asthma in children and adults. Rhinoviruses were the major pathogen implicated, and the majority of viral infections and asthma admissions occurred during school attendance, according to the study byÂ the Department of Medical Statistics and Computing, University of Southampton(15).

9. Irregular Mentruation
Irregular menstruation are associated with asthma. In the study of a total of 8588 women (response rate 77%) participated in an 8 year follow up postal questionnaire study of participants of the ECRHS stage I in Denmark, Estonia, Iceland, Norway, and Sweden. Only non-pregnant women not taking exogenous sex hormones were included in the analyses (n = 6137), showed that Irregular menstruation was associated with asthma (OR 1.54 (95% CI 1.11 to 2.13)), asthma symptoms (OR 1.47 (95% CI 1.16 to 1.86)), hay fever (OR 1.29 (95% CI 1.05 to 1.57)), and asthma preceded by hay fever (OR 1.95 (95% CI 1.30 to 2.96)) among women aged 26-42 years(16).

10. Sulphite additives
Topical, oral or parenteral exposure to sulphites (mainly from the consumption of foods and drinks that contain these additives)Â has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions(16a).

11. Cold air
Endurance athletes show an increased prevalence of airway hyperresponsiveness. In the study of aÂ total, 64 elite athletes (32 swimmers and 32 cold-air athletes), 32 mild asthmatic subjects and 32 healthy controls underwent allergy skin prick testing, methacholine challenge and induced sputum analysis found that there is aÂ significant airway inflammation only in competitive athletes with airway hyperresponsiveness. However, the majority of elite athletes showed evidence of bronchial epithelial damage that could possibly contribute to the development of airway hyperresponsiveness(17a).

11. Etc.Â

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Asthma remedies to quickly and safelyÂ
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For common types of diseases of Ages of 50+, please visit http://medicaladvisorjournals.blogspot.ca/p/better-of-living-health-50-over.html

For other health article, visit http://medicaladvisorjournals.blogspot.caÂ Â Â Â

Saturday, September 21, 2013

Syndrome of aspirin-exacerbated respiratory disease (AERD)

According to the study of Prostaglandins and leukotrienes as inflammatory mediators by John A Salmon and Gerald A Higgs(a), Leukotrienes is produced in leukocytes as a result of oxidative metabolism of arachidonic acid by the enzyme arachidonate 5-lipoxygenase, belonging to the family of eicosanoid inflammatory mediators(a). Its production is usually accompanied by the production of histamine and prostaglandins.
Syndrome of aspirin-exacerbated respiratory disease (AERD)
Chronic rhinosinusitis (CRS) with nasal polyposis (NP) may be associated with hypersensitivity to nonsteroidal anti-inflammatory drugs, representing a syndrome of aspirin-exacerbated respiratory disease (AERD). According to the study by the Jagiellonian University Medical College, among CRS subjects requiring functional endoscopic sinus surgery (FESS), as many as 33.3% may have AERD and respond to a small provocative dose of aspirin with bronchoconstriction and/or mucosal and skin edema. A simple and inexpensive measurement of uLTE4 (leukotriene E4)Â can help diagnose AERD in patients with CRS with sensitivity of 87.5%, but its specificity is limited and depends on the arbitrary threshold of uLTE4(25).
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Sources

(a) http://bmb.oxfordjournals.org/content/43/2/285Â Â Â
(25) http://www.ncbi.nlm.nih.gov/pubmed/22814420Â

Thursday, September 12, 2013

New FDA Policy Endangers Respiratory Patients

“…Your inhaler may be changing.”

This is the quasi-advertising slug that has been making the medical community rounds for the past year or so. If youâ€™re one of the 10 million Americans living with asthma, you may have seen it. But what you probably donâ€™t know is that this change could actually kill you.

Earlier this year, the US Food and Drug Administration made the first major alteration in decades to all aerosol respiratory illness medications in this country by replacing the standard CFC aerosol propellants with a new propellant formulation known as â€œHFA”. The change was made across the board — CFCs were replaced by HFA without any alternative.

So what’s wrong with switching CFCs to HFA? According to the growing preponderance of anecdotal evidence at The National Campaign to Save CFC Inhalers, HFA is making far too many people very, very ill. Reported problems with HFA inhalers run the gamut from â€˜my medication doesnâ€™t seem to be working as wellâ€™, to causing major upper respiratory and even system-wide infections requiring hospitalization and months of recuperation.

Rescued by an Inhaler

It goes without saying that the FDA is supposed to be tasked with ensuring the safety of all prescription medications. In the United States alone, more than 35 million chronic respiratory patients depend on FDA-approved prescription inhaled medications to achieve a reasonable quality of life. Diseases that make up the chronic respiratory category include asthma as well as COPD (chronic obstructive pulmonary disease), emphysema, tuberculosis, cystic fibrosis, lung cancer, pneumonia, and aspergillosis.

For the majority of the above patients, albuterol (also called salbutamol) has been the drug-of-choice in an emergency situation for decades. Most patients carry albuterol â€œrescue inhalersâ€ with them at all times. Rescue inhalers mean a world of difference in a personâ€™s day-to-day quality of life. Almost all respiratory patients will unfortunately have an emergency of the type rescue inhalers are designed to address. For some reason or another, their illness suddenly becomes extremely acute and immediate medication intervention is required no matter where the patient is at the time. With a simple rescue inhaler on hand that works, the acute condition of the moment is usually resolved before major medical care is required. Without a rescue inhaler that works as advertised at that moment, hospitalization and even death is a possibility.

Albuterol CFC rescue inhalers have provided this service consistently, and patients have been able to trust this medication to work for decades. The wholesale change to HFA by the FDA leads one believe that the FDA has rigorously determined that the new inhalers will do likewise. But in practice, are HFA rescue inhalers working when a patient really needs them — in a major breathing emergency? The growing evidence is “no”, but pinning down just how well HFA does perform has been difficult due to the broad range of patient complaints.

It isn’t surprising there are so many nebulous complaints regarding the effectiveness of HFA inhalers. Itâ€™s hard to determine if someone is having adverse reactions to HFA because at the same time one is breathing in the propellant that might be an irritant, one is also breathing in the medication that counteracts the symptoms of the irritation. Just how well the medication masks an irritating effect from the propellant can vary wildly from person to person, and from moment to moment. If a person is pretty healthy, they might not notice the irritant much. However, if someoneâ€™s immune system gets run down by an illness or stress, normal “irritants” tend to get more irritating at an almost exponential rate.

Unless cause and effect is very clear, after using an HFA inhaler the patient doesnâ€™t know what factors have combined in what amount to make them breathe as well as they are at that moment. Many patientsâ€™ complaints with HFA stem from a simple comparison of their old CFC inhalers with the new ones. Some complaints arise when a patient actually goes into anaphylaxis due to using an HFA inhaler. Often their life was saved by an old CFC inhaler that happened to be nearby.

There is very little hard scientific data on HFAs vs. CFCs in actual respiratory patients because the majority of the published clinical data was done on healthy people — people for whom lung irritation is not an issue. However, in a UK field study done at the time albuterol/salbutamol HFA inhalers were released in the United Kingdom, MDs monitoring their use by actual respiratory patients found that four times the number of patients who had trouble tolerating CFC inhalers were made ill by HFA. (CFC intolerance is less than 1% of the patient population.) That makes at least one fact-based HFA intolerance estimate around 4%, or 1.4 million Americans. This number is probably low since understanding of just what problems are being caused by HFA verses normal external influences werenâ€™t even under consideration at the time.

Midway through this year, most major pharmacies and mail order services have already switched to the FDA-approved HFA replacements exclusively, leaving patients who are having trouble with HFA inhalers to scramble for the remaining CFC inhalers on the market. According to FDA mandate, all CFC inhaler production must cease on December 31st, 2008 leaving HFA-sensitive patients without any legal options.

The War Over CFC Replacement

Albuterol inhalers have been available as generics in the in the US for decades. This medication alone was a $ 400 million dollar annual business even then. The CFC phase-out was an obvious opportunity for drug companies to return the medication’s new formulation to a patented status. Which ever company(ies) got their hand of the FDA’s approved replacement stood to find themselves with a huge cash cow in the making.

(article continues after break)

The political struggle over which large US pharmaceutical company would get the lucrative monopoly on CFC replacements started more than a decade ago. There are two types of inhaler technology currently in use worldwide: â€˜metered dose inhalersâ€™ [MDIs] that require a propellant, and â€˜dry powder inhalersâ€™ [DPIs] that use turbulent air flow caused by the patient breathing in to disperse the medication â€“ this means no propellants are needed. Glaxo Smith-Kline was fast off the mark, introducing an albuterol DPI under the brand name Ventolin Rotacaps in 1989. Clinical studies found Ventolin Rotacaps as efficacious as their CFC counterparts.

So what happened to Glaxoâ€™s Rotacaps system? It lost out in the ensuing political dog fight and Glaxo discontinued production everywhere in 2003. When the fur finished flying, the FDA approved four â€œbrandedâ€ albuterol MDIs only. Schering-Plough has been the biggest winner so far. Their Proventil HFA has absolutely dominated rescue inhaler sales in the United States this year. Today, albuterol has not only been moved from generic back to proprietary and the financial cost to patients tripled or quadrupled, but there will be no legal alternatives to HFA in the United States come January 1, 2009.

HFAs vs. CFCs in the Environment

It’s been fairly universal knowledge that chlorofluorocarbons are “bad” for decades, but the reasons why are a complex mix of chemistry and physics. There are a number of published theories involving the exact photochemical processes by which CFCs produce damage to the protective, UV-blocking ozone [O3] layer of the Earthâ€™s atmosphere. It’s safe to say that today in 2008, most of the scientific community believes that CFCs are still a major contributor to the infamous O3 â€œholeâ€. The public education campaign against CFCs dates back to 1987, when the Montreal Protocol on Substances that Deplete the Ozone Layer was enacted. At that time, worldwide CFC emissions were on the order of 1.2 million tons per year. However, the medical use of CFCs has been almost negligible since it began to be measured. At peak use, CFC inhalers have accounted for a maximum of just 0.83 % of the 1987 total. In the United States, CFC inhalers account for less than 0.3 % annually.

Itâ€™s political and career suicide to fight the â€œall CFCs badâ€ paradigm. Yet, there are scientists and learned folks out there who have quietly run their numerical models with the result that CFC MDI use has no appreciable degrading effect on the ozone layer. Getting them to speak up has been no easy matter.

When the Clean Air Act was updated in 1991 to address the Montreal Protocol, chlorofluorocarbons in aerosols were slated to be phased out world-wide by 2010, including when being used in medical necessities. The assumption was that technology would provide a new propellant as good as or better than CFCs before the drop-dead date was reached. Itâ€™s now 2008, and the new technology lung patients are forced to accept is HFA or the highway â€“ there are no alternatives.

Making matters worse, ethanol — a toxic, Class 3 residual solvent produced from corn and known to cause the actual constriction of airways in lung patients — is added to three of the four most common HFA rescue inhalers in amounts varying from 10%-14% by weight. Yet the FDA has issued assurances that the ethanol in HFA inhalers is present in amounts too small to cause any danger. So just how much is too small? Ask the person who nearly dies from anaphylaxis because the snack they just ate doesnâ€™t contain peanuts but may contain ingredients from a plant that processes peanuts.

And what about DPIs? With no propellants needed, it might seem like DPIs are the best solution to the problem of getting respiratory patients their medication. Unfortunately, there are millions of Americans whose normal day-to-day lung function is not strong enough to breathe deep enough to make a DPI effective for them. MDIs, and therefore propellants, are necessary.

Fighting the Government to Breathe in 2009

When all is said and done, the bottom line is that until the FDA acknowledges the HFA debacle and approves another form of albuterol MDI, the average respiratory patient cannot rely on HFA products for a rescue inhaler. To be truly safe, patients should always carry a nebulizer — a mechanical air pump that disperses liquids for aspiration — with liquid albuterol or epinephrine ampules for emergencies. Comparatively, nebulizers are big, bulky, and inconvenient…. and if toting a nebulizer around everywhere won’t be making a serious a dent in your quality of life, who knows what does.

Meanwhile, albuterol DPI rescue inhalers are available by other manufacturers throughout the rest of the civilized world except North America for literally pennies on the dollar that Schering Plough is making with Proventil HFA.

Respiratory patients who want to fight back find themselves facing the some of the biggest, ugliest and nastiest bureaucracies, monopolies and politicos out there: the FDA, the EPA, the US pharmaceutical money-making monster, and even the Corn lobby-from-hell. The battle may look impossible, but this is about the quality of life, and possibly even death for 35 million Americans.

If you or someone you know wants to fight back, The National Campaign to Save CFC Inhalers is a great place to start.

Just Transition â€˜Em

Finally, according to this slick and likely expensive Patient HFA Transition Guide for MDs, there are just four simple steps to transitioning all respiratory patients to HFA inhalers:

1. IDENTIFY patients that currently use CFC bronchodilators.
2. INITIATE discussion and inform patients of their HFA treatment options.
3. INSTRUCT patients about new use and care directions.
4. TRANSITION your patients.

Amazingly simple, isn’t it?

Labels: albuterol, asthma, clean air act, food and drug administration, HFA, Montreal protocol, national campaign to save CFC inhalers, Ozone layer, Proventil, Ventolin

Wednesday, September 11, 2013

Most Common Diseases of Age 50+: Asthma (Respiratory Disease) - The Complications

D. Complications
1. Quality of life
In a cross-sectional study explored the relationships among family ritual meaning, cohesion, conflict, and health-related quality of life (both specific to chronic health conditions and in general), and the emotional and behavioral problems reported by youths with asthma, conducted by Faculty of Psychology and Educational Sciences, University of Coimbra, showed that stronger family ritual meaning predicted a more positive family environment (i.e., higher cohesion levels and lower conflict levels), better health-related quality of life, and fewer emotional and behavior problems in youths. Furthermore, family cohesion and conflict mediated the links between family ritual meaning and health-related quality of life, and emotional and behavioral problems(34). In 2007â€“08, people with asthma were more likely to have taken days off work, school or study in the last 12 months due to a long term condition than people without asthma (although these days off were not necessarily due to asthma). People with asthma rate their health worse than people without the condition, according to the data ofAIHW(35).

2. Corticoid-associated complications
In the stduy to evaluate the frequency and type of side effects and complications of long-term corticosteroid therapy in the elderly, showed that infectious complications were found in 26 cases (39.3%), 11 cases (16.7%) of iatrogenic diabetes, arterial hypertension in 9 cases (13%), skeletal complications in both cases,psychiatric complications in two cases, ophthalmologic complications in one case(36).Â

3. Subcutaneous and mediastinal emphysema
There is a report of a case of a 21-year-old man admitted with asthma attack complicated by subcutaneous and mediastinal emphysema. Chest tomography confirmed the mediastinal emphysema and also revealed the epidural emphysema within the vertebral canal(37).

4. Pneumomediastinum
There is a report of a 17-year-old girl with severe asthma exacerbations. On admission to the intensive care unit, she manifested expiratory dyspnea, cyanosis, and an unproductive cough. Her chest x-rays showed extensive pneumomediastinum (PM), mild subcutaneous emphysema at the right anterior triangle of the neck, and right upper-lobe atelectasis(38).Â

5. Respiratory complications

Children with asthma are at increased risk for obstructive breathing during sleep. Adenotonsillectomy, the treatment of choice for obstructive breathing during sleep, is associated with significant postoperative respiratory morbidity. According to the study by Cincinnati Children’s Hospital, Cincinnati, in children with obstructive breathing during sleep, the presence of asthma is associated with an increased risk of respiratory complications after adenotonsillectomy(39). Other indicated that the frequency of perioperative bronchospasm and laryngospasm was surprisingly low in this cohort of persons with asthma. These complications did not lead to severe respiratory outcomes in most patients. The frequency of complications was increased in older patients and in those with active asthma(40).

6. Potentially (near) fatal asthma (PFA)
Potentially (near) fatal asthma (PFA) defines a subset of patients with asthma who are at increased risk for death from their disease. According to the study by the Northwestern University Feinberg School of Medicine, a diagnosis of PFA is made when any one of the following are present: (1) history of endotracheal intubation from asthma, (2) acute respiratory acidosis (pH < 7.35) or respiratory failure from acute severe asthma, (3) two or more episodes of acute pneumothorax or pneumomediastinum from asthma, (4) two or more episodes of acute severe asthma despite the use of long-term oral corticosteroids and other antiasthma medications.
In the UK in 2005, over 1300 people died from asthma, and on average one person dies from asthma every seven hours.

7. Etc.

Â Asthma Relief
Asthma remedies to quickly and safelyÂ
eliminate my own asthma & allergy symptoms

For common types of diseases of Ages of 50+, please visit http://medicaladvisorjournals.blogspot.ca/p/better-of-living-health-50-over.html

For other health article, visit http://medicaladvisorjournals.blogspot.caÂ Â Â Â

Sources Â Â
(1) http://www.ncbi.nlm.nih.gov/pubmed/9643741Â
(35) http://www.aihw.gov.au/asthma-quality-of-life/
(36) http://www.ncbi.nlm.nih.gov/pubmed/23197053
(37) http://www.ncbi.nlm.nih.gov/pubmed/23182721
(38) http://www.ncbi.nlm.nih.gov/pubmed/20561891
(39) http://www.ncbi.nlm.nih.gov/pubmed/15945558
(40) http://www.ncbi.nlm.nih.gov/pubmed/8853074Â

signs of asthma