Respiratory Diseases: Chronic Obstructive Pulmonary Disease (COPD)- Part II

(5/19/07)- According to the latest estimates from the National Institutes of Health's National Heart, Lung and Blood Institute (NHLBI) there are an estimated 24 million Americans with COPD, about half of whom remain undiagnosed. The NHLBI along with a number of non-profit groups and medical specialty societies are instituting a campaign to raise the public's awareness about the disease.

The aim of the campaign is to encourage people over 45 who may be at risk to get a simple breathing test and talk to their doctors about treatments that can slow or even reverse the disease.

COPD is a term used for lung diseases that inflame airways, obstruct breathing and trap bad air in the lungs. It is the 5th largest cause of death in the world, while in the U.S. it is the 4th ranked killer behind heart disease, cancer and stroke, and it costs an estimated $40 billion a year.

To learn more about the disease go to: or

The COPD Foundation, in partnership with the American Association of Respiratory Therapists is sending a mobile testing unit to a number of cities across the country offering free spirometry, a lung function test that measures the amount of air a person can breathe out and the time it takes to do so. Hand held version of the device can cost as little as $500 to $800, and it is considered the gold standard for an initial diagnosis of COPD.

There are several drugs used to treat the disease, which though incurable can be prevented from worsening. Spiriva, an inhaler which is also known as tiotropium is the most commonly used medication. Advair, which is a combination of the steroid drugs fluticasone and salmeterol is another inhaler type medication used against COPD.

A study in the May issue of the American Journal of Respiratory and Critical Care Medicine found that a promising anti-inflammatory drug, infliximab, failed to improve symptoms of moderate to severe COPD

10/11/02)-The following are two e-mails that we received at therubins recently on this topic and Harold's response to both of them. We encourage all our viewers to e-mail us with any questions that they may have about the subjects that we write about, and we will do our best to reply as promptly as possible.

e-mail #2-

I have been diagnosed with COPD and have been on many medications in the last 3 years trying to find one or more that work. I was taking FORADIL and COMBIVENT together and have now developed neck and ear pain on the left side.I tried ADVAIR ( all types) and developed a limp and loss of strength in my left arm while using it. At first I thought I had the start of PARKINSONS,but I can stop any shakiness I have at will. Also I have now been told that while using FORADIL you should not take anything else but a steroid possibly. Have you ever heard of any of these symptoms and what are your thoughts on the safety of SPIRIVA?

Thanks, W.A.,Michigan

Response from Harold Rubin

Dear W.A.
Thank you for viewing our web site. We attempt to provide information to our readers that could be of help in enhancing their quality of life. We are not physicians or pharmacists, but we do a lot of research in the medical field and provide the most current information available to us for you to read and make your own judgments. This is a public service site and we would appreciate your telling others of its existence.

Have you told your treating physician about the side effects you are experiencing? He/she is the best person to help you in determining what are the adverse effects of the medications you are taking and what may be concomitant morbid conditions. This is an essential step in your treatment regimen. Secondly, if you feel the symptoms were related to the medication you were taking, this should be reported to the FDA by you or your doctor. There is a standard form for reporting adverse effects. (Because of the expenses involved in long term research study of medication, among other factors, few are done. This makes it essential for users to report any untoward effects and for some people to wait, if it is possible, more than a year before starting to take the new medication.)

Now as for spiriva and COPD:
COPD is a slowly progressive airway disease that causes significant deterioration of lung function and consequently, disability and death. Smoking is the leading cause of COPD, but exposure to pollution and genetic predisposition are other known risk factors. It mainly effects middle-aged and elderly people. While it is less well known than asthma, COPD is in fact more prevalent. According to the World Health Organization, about 600 million people suffer from COPD, although many are undiagnosed. Estimated prevalence in the United States has risen by 41% since 1982. Airway obstruction is usually progressive to those who continue to smoke. Many people will need medication for the rest of their lives, with increased doses and additional drugs during exacerbations.

Spiriva has the active substance tiotropium bromide, which is a new chemical entity, structurally related to ipratropium bromide (Atrovent ®). Tiotropium is a long-acting inhaled antimuscarinic bronchodilator.

The capsules are to be administered (once daily) with the HandiHaler® inhalation device that enables extraction of the dose from the capsules and dispersion of the drug substance in the inhalation airstream of the patient.

Tiotropium, discovered and developed by Boehringer Ingelheim, is a novel compound that works through prolonging M3-receptor antagonism. It is a long acting, specific, muscarinic receptor antagonist, which binds to the muscarinic receptors in the bronchial smooth musculati=ure inhibiting the cholinergic effects of acetylcholine released from parasympathetic nerve endings. It has similar affinity to the subtypes of muscarinic receptors. It reversibly antagonizes the M3 receptors resulting in relaxation. Effect is usually within 30 minutes following the first dose and is maintained for 24 hours. It reaches its psychodynamic steady state within one week. No long term studies exist. (Longest we are aware lasted one year.). When approved, tiotropium will be the first once-daily inhaled treatment for COPD. Earlier this year, Boehringer Ingelheim and Pfizer Inc. announced that they have entered into a long-term worldwide agreement to co-promote tiotropium.

A FDA advisory panel is set to review a marketing application for Spiriva (tiotropium bromide) for the treatment of chronic obstructive pulmonary disease (COPD). Spiriva, an anticholinergic compound, is the first once-daily inhaled therapy for COPD. The drug was first registered in The Netherlands in October 2001 and is currently being rolled out in markets throughout the European Union. Boehringer Ingelheim has said that it anticipates launching the drug in the UK this week. There was to be a hearing on the drug in the beginning of Sept. 2002 held by the FDA.

We can tell you the following things about the drug:
Precautions: 1. Contraindicated in individuals with hypersensitivity to tiotropium bromide, atropine or its derivatives e. g. iprratropium or oxitropium or to the eccipient lactose monohydrate.
2. Should be used with caution in individuals with narrow angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.
3. It may cause induced bronchospasm
4. In individuals with decreased renal function, it should be used with caution (weigh risk-benefit potential). (Remember decreased renal function is a not uncommon symptom associated with aging)
5. Do not get the drug powder into your eye as it can lead to eye pain, temporary blurring of vision, colored images in association with red eyes from conjunctival and corneal congestion.
6. Dry mouth may in the long run be associated with dental caries.
7. There are no formal drug studies involving interaction with other drugs especially with anticholinergic drugs.

Undesirable Effects: In a study of 906 patients, about 14% reported dry mouth as the most common adverse reaction. Other side effects include constipation, sinusitis, pharyngitis and moniliasis as well as urinary retention. Rare side effects included supraventricular tachycardia and atrial fibrillation.

We hope this information is of help to you. Please remember that treatment is also dependent on the stage of the disease, the age of patient, the length of time the medicine is to be taken, the idiosyncratic adverse effects of medications on individuals.

If you have a medical school near where you reside, check to see if you can get the journal called "Clinical Evidence" 2002;7: 1344-1357. There is an article entitled Chronic obstructive pulmonary disease written by Huib A. Kerstiens, MD., Ph.D., And Dirkje S Postma, MD., Ph.D. (University Hospital Gronigen, Gronigen, The Netherlands) that is quite technical but informative.

Please let us know if we can be of further help to you.

Harold Rubin

e-mail # 1

My Father was prescribed advair for copd. I would appreciate any information you can give me on this drug ie. How long has it been used, what kind of studies have been done on this drug. Also any information you can give me on new and possible new drugs that is being tested for this disease.

Thank you for your time

Response from Harold Rubin

Dear Sir:

For information on Advair, please go to the site or put the word advair in your keyword box and you will get a list of sites providing information on this drug.

As an aside, I presently am a daily user of flovent and serevent for my bronchial asthma. My doctor has suggested to me that I switch to advair because it combines the two inhalers I am presently using. I plan to switch to it when I use up my present supply of flovent and serevent.

I hope this gives you a start in finding the information you want. If we can be of any further help, feel free to email us. We hope you will continue to check our web site for information.

Follow-up to the prior answer from Harold Rubin

As you may know, COPD stands for Chronic Obstructive Pulmonary Disorder. We are not aware of who first attributed this title to the disorder.

COPD is the terminology for two disease states: chronic bronchitis and emphysema. COPD is a clinical diagnosis defined as obstruction of the airways of the lungs of a persistent non-reversible nature. The formal definition of chronic bronchitis is a productive cough that lasts for three months during two consecutive years. Emphysema, clinically characterized by obstruction to airflow, is defined pathologically as destruction of alveolar walls causing enlargement of distal air spaces. These conditions share a common characteristic- chronic limitation to expiratory flow. Most patients with emphysema have components of chronic bronchitis as well. Some physicians will include asthma in the categorization of COPD, but pure bronchospastic asthma is rare in the elderly.

COPD effects more than 4 million people in the US; it is the second leading cause of disability (after back pain) and the fourth most common cause of death in adults. It is responsible for more than 14 million office visits and 500,000 hospitalizations per year, and it is the third most frequent justification for home care service.

I did some further research in an attempt to answer your question and can give you the following information: It was Laennec who in 1819 recorded the clinical features associated with the disease, including dyspnea, hyperresonance, faint breath sounds and wheezes. See; Rosenblatt, MB. Emphysema in the 19th century. Bull Hist Med 1969; 43:533-552.

We hope this is the type of information you are looking for. If we can be of further help, please do not hesitate to contact us.


Harold Rubin

June 17, 2002

The FDA's pulmonary disease advisory panel voted to approve GlaxoSmithKline's Flovent, an inhaled steroid which reduces lung inflammation, and Advair which combines a steroid and bronchodilator to open the airways, for use in chronic obstructive pumonary disease (COPD). It will take a while before the recommendation of the advisory panel is acted on by the full committe, but we expect such action to take place shortly.

Chronic obstructive pulmonary disease (COPD) is defined as obstruction of the airways of the lungs of a persistent non-reversible nature. It is a generic term that includes chronic obstructive bronchitis, emphysema, and asthmatic bronchitis. It is estimated that COPD effects 14 million people in the USA and is the second leading cause of disability after back pain. It results in over 500,000 hospital visits per year. The cost to society is tremendous, not to overlook the deadly cost to the individual.

While advances have been made in treating of COPD, there are no quick cures and response to therapy is often marginal, with indications that those individuals who have an advanced stage of the disease have marginal chances for survival. With this said, there are indications that new procedures are on the horizon that would make this outcome not as deadly as it is now. These include new bronchodilators and anti-inflammatory agents as well as lung transplantation and lung reduction surgery.

The current "gold standard" for treating COPD is Atrovent which is a drug that has to be taken 4 times daily. The drug is made by Boerhinger Ingelheim (BI) which is the global leading drug company for drugs that treat COPD. Sales in 1999 for BI two leading COPD drugs Atrovent and Combivent totaled $970 million. A new drug from BI, which will be co-marketed, with Pfizer named Spiriva is on the horizon that may become the number one drug in treating COPD. Spiriva will only have to be taken once a day. In two head-to-head studies, Spiriva demonstrated better efficacy the Atrovent, and at a price of $2 a day is much cheaper than Atrovent. Spiriva could be approved in Europe as early as mid-2002 and in the U.S. about late 2002.

Symptoms of COPD develop slowly, usually manifesting themselves between forty and fifty years of age. Predominant symptoms include cough, sputum production and dyspnea. Chronic bronchitis is diagnosed as a productive cough that lasts three months during two consecutive years and hypersecretion of mucus.

Emphysema is defined as destruction of alveolar walls causing enlargement of distal air spaces. Both result in chronic limitation of expiratory airflow. In fact, the American Thoracic Society uses forced expiratory volume in the first second of breathing on a spirometry machine as its definition of the severity of the different stages of COPD. It is also used to predict longevity and improvement after brochodilator therapy. A naturalistic study done in 1977 by Fletcher and Peto found that nonsmokers and those not subject to the effects of cigarettes lost about 20-30 ml of forced expiratory volume per year, while smokers with airway obstruction suffered a decline of 40-80 ml per year. (Fletcher C & Peto R. The natural history of chronic airflow obstruction. British Medical Journal 1977; 1645-1648.)

As we age, the lung undergoes a loss of elasticity and a gradual loss of aveolar units and the creation of air sacs units within the lung. This in itself is not enough to cause the disease as the lung has sufficient reserve to sustain function throughout a lifetime without any clinical symptoms.

However, risk factors such as cigarette smoking, occupational dust, second hand smoke, airway hyper-responsiveness, infection and an anti-trypsin deficiency appear to enhance disease. Large air sacs appear which create a respiratory system that traps air, prevents normal expiratory forces from expelling air and with loss of aveolar units impairs the extraction of oxygen within each air space.

A barrel-like chest cavity develops as result of the over-expansion of the pulmonary structure. The result is a decline in the function of the respiratory muscles and a rise in carbon dioxide levels. This cycle is worsened by mucus blockade and airway inflammation that causes severe difficulty in breathing.

While cigarette smoking is the main risk factor for developing COPD, only about 10-15% of people who smoke develop COPD. Researchers still do not understand why this population is susceptible to lung injury from tobacco use. Epidemiologists attribute 80-90% of the deaths from COPD to smoking. (Davis RM & Novotny TE. The epidemiology of cigarette smoking and its impact on chronic obstructive pulmonary disease. Am Dev Respir Dis 1989; 140:582-584.)

Management of COPD is designed to limit the decline in respiratory function over time. Stopping of smoking is a primary goal that has been achieved with some success through behavioral modification programs as well as pharmacological interventions. Since respiratory infections can effect the lungs, regular vaccinations for flu are important. Regular use of a brochodilator can ease the symptoms of COPD and thus improve the functional capacity of the individual. It goes without saying that measures such as exercise and nutrition that improve the general health of the individual are essential treatment modalities. Oxygen is administered in situations of hypoxemia and antibiotics are used during acute infectious stages.

For further information on diagnosis and care of patients with COPD we suggest you talk to your physician, contact the American Thoracic Society or read volume 153 of the American Journal of Respiratory and Critical Care Medicine (1995) in which they discuss the severity stages of COPD.

For Respiratory Infections Part I: A Hidden Killer of the Elderly
Pulmonary Rehabilitation for COPD-Part III



Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated May 19, 2007

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