A Cure for Asthma?: What Your Doctor Isn't Telling You--and Why

antibiotic.

PREFACE

Jim Quinlan lay dying on his front porch. The strangler had brought him down as he neared home. After it was over, the photo that ran in the local paper showed a rescue squad ranged on the porch. The story recounted his resuscitation and, thankfully, survival.

He could have torn a human’s hands from his windpipe, but his attacker had not been human. Jim Quinlan had asthma.

His doctors told him there must be something in the environment triggering his attacks. So he moved from Michigan to Florida. But he took his asthma with him. His doctors told him he had an incurable disease. But he refused to believe them. He searched the Internet for a cure for asthma. He combed through a lot of misinformation. Eventually, he contacted me.

Jim convinced his doctor to prescribe the prolonged antibiotic treatment that I recommended. Some years after Jim and I spoke, a different local paper ran a story about Jim Quinlan. He was hiking the Appalachian Trail—without asthma medicine, and without asthma symptoms.

Even now, over 15 years later, Jim no longer suffers from asthma.

Jim is one of millions of Americans with severe—even life-threatening—asthma that is not well controlled by conventional asthma medicines. These medicines suppress symptoms, but they do not cure asthma. The primary guideline medicine is corticosteroid treatment—mainly inhaled corticosteroids (ICS), but for the most difficult cases, oral corticosteroids (OCS) are also prescribed. ICS have significant side effects and risks: sore throat, hoarseness, yeast infections, cataracts, glaucoma, osteoporosis, and growth retardation in children.¹ For OCS, add: obesity, hypertension, diabetes, electrolyte disturbances, adrenal suppression, insomnia, and more infections, including tuberculosis.

Here is a secret that most asthma experts know, but that the general public does not: existing treatments that conform to the guidelines don’t work for many people with asthma. Why not? And why aren’t scientists vying to conduct innovative research that would yield better treatments, with fewer side effects and risks? There is a candidate for better treatment for such people, but it has been largely neglected for nearly 20 years. Emerging evidence shows that the most severe and steroid resistant forms of asthma are related to treatable infections. That is what Jim Quinlan discovered more than 15 years ago.

Now, thanks to the Internet, a growing number of people with poorly controlled asthma are asking their doctors for this antibiotic treatment. Many of them are being turned down. Why? Because asthma experts and the guidelines they write do not acknowledge that infection may be a treatable cause of asthma. Therefore, most prescribers are unaware of evidence demonstrating that antibiotic treatment has proven successful for many people with asthma when all other methods have failed. Instead, they pile on the steroids and other guideline medications, causing more and more side effects and risks with little or no additional benefit.

If you suffer from poorly controlled asthma, I wrote this book with you in mind. If you are a practicing physician and want to help patients suffering from steroid-resistant or poorly controlled asthma, I wrote this book for you, too. If you are an asthma expert concerned about a lack of patient-centeredness in your research, this book may interest you, too.

This is a book of stories. The first section tells the stories of asthma patients—children, teens, and adults from across North America—writing in their own words or the words of their parents. All of them suffered from new-onset or poorly controlled asthma. They either were my patients, or they reached out to me for help when they couldn’t find it elsewhere. Many of them experienced drastic alleviations of their asthma symptoms or even total remission after taking a course of an antibiotic called azithromycin.

The second section, Evidence, also centers on stories: scientific narratives that impose structure on complex data about cause, effect, treatment, and cure. I approach these evidentiary stories first from the perspective of a laboratory scientist, and then through the lens of an epidemiologist studying people in the community. In this section, I summarize the emerging scientific evidence that infection is a treatable cause for asthma. This particular story needs more chapters before we can know its conclusion. My hope in writing this book is to encourage the research required for us to know the story’s outcome. This section also includes experimental evidence that infection can promote both asthma and allergies. If true, this could explain otherwise puzzling early epidemiological observations that allergies can happen during the onset of asthma, or even afterwards, but usually not before.²

In the third section, Challenges, I try to address the question of why experts have largely failed to engage with this emerging evidence for nearly two decades and have not initiated enough meaningful research into a potential breakthrough treatment.

Finally, in the fourth and last section, Solutions, I present my own guidelines for people with asthma who want to take advantage of antibiotic treatment now. And I also outline neglected research approaches that I hope will lead to better scientific evidence to support stronger asthma guidelines in the future.

You deserve to be informed about all the evidence available on your condition so that you can apply your own values to decisions regarding your health. Right now, when it comes to asthma treatment, the doctor does not always know best.

Annotated Bibliography

1. ICS treatment reduces the height of all children over age three by half an inch on average. And yet for recent-onset mild persistent asthma, it prevents an asthma attack in fewer than 1 in 100 children per year.

Kelly HW, Sternberg AL, Lescher R, Fuhlbrigge AL, Williams P, Zeiger RS, Raissy HH, Van Natta ML, Tonascia J, and Strunk RC. Effect of inhaled glucocorticoids in childhood on adult height. N. Engl. J. Med. 2012; 367:904-912.

Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen Y-Z, Ohlsson SV, Ullman A, Lamm CJ, O’Byrne P. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361:1071-1076.

2. Broder I, Barlow PP, Horton RJM. The epidemiology of asthma and hay fever in a total community, Tecumseh, Michigan. II. The relationship between asthma and hay fever. J Allergy 1962; 33:524-531

This is one of the earliest studies of asthma and hay fever in a total community.  The authors found that asthma and hay fever happened in the same individual more often than was expected by chance (this is called an association).  And they wrote, If this frequent association were on the basis of hay fever being followed at a later time by asthma, there are several relationships which the available data might be expected to show, but do not...Of persons in whom the onset sequence was known, either asthma was present alone intially or the two diseases began within the same year of age in approximately 75 percent. 

There is also more recent evidence questioning the established wisdom that allergies and asthma are virtually the same thing.  Perhaps the most notable is a review written by the original proponent of the hygiene hypothesis (Dr. David Strachan).  The hygiene hypothesis refers to the theory that exposures to infections early in life protect against allergic diseases, and that good hygiene (i.e., not getting lots of infections) is a risk factor for becoming allergic.  In his review, Dr. Strachan found that data support the hygiene hypothesis more with respect to hay fever and less (if at all) with respect to asthma (see: Strachan DP. Family size, infection and atopy: the first decade of the hygiene hypothesis. Thorax. 2000; 55 (Supplement 1): S2-S10.)

INTRODUCTION

In the late 1980s, while I was conducting a study on a new bacterial cause for bronchitis and pneumonia, I enrolled a 45-year-old woman whom I’ll call Susan. She’d come down with acute bronchitis and had started wheezing for the first time in her life. Her blood tests confirmed that she had an acute (first) infection with Chlamydia pneumoniae, which was the cause of her acute asthmatic bronchitis.¹ When I first met Susan, researchers had only just discovered that C. pneumoniae, a so-called atypical bacterium, could cause acute bronchitis and community-acquired pneumonia.² (see Chlamydia Pneumoniae).

Acute asthmatic bronchitis is quite common. Usually, the affected patient’s wheezing goes away as the illness spontaneously subsides.¹ Instead of going away, however, Susan’s wheezing got worse, and she began requiring daily asthma medications. Finally, after she had suffered six months of debilitating daily wheezing, chest tightness, and shortness of breath, I referred Susan to one of my partners, a pulmonologist, who performed pulmonary function tests on her. He diagnosed asthma. But despite his treatments, it continued to bother her. By that point, she had also developed persisting high levels of antibodies against C. pneumoniae.

Around the time I referred Susan, I began to notice that almost every wheezing person we had enrolled in our cough study had unusually high levels of C. pneumoniae antibodies. Wheezing was such a reliable symptom, in fact, that I could usually use it to predict when antibody levels would be high. It occurred to me that Susan’s antibody levels had been negative before her illness, but had risen afterwards, and had remained persistently elevated. So I got in touch with her to present a hypothesis: perhaps the Chlamydia infection that had led to her first bout of wheezing had never gone away and was now causing her asthma symptoms.

Chlamydia pneumoniae

What is Chlamydia* pneumoniae?

The first question I often get asked when I mention Chlamydia pneumoniae is: do you mean I have a sexually transmitted disease? The answer is no. Chlamydia pneumoniae causes lung and breathing problems and is not transmitted sexually. The infamous STD is caused by Chlamydia trachomatis, a completely different species. C. trachomatis can also cause diseases such as blindness and arthritis, though it has also been associated with asthma in children.³

C. pneumoniae is similar to C. trachomatis in that it has been associated with a variety of chronic illnesses: not just asthma and other respiratory conditions,⁴ but also coronary artery disease.⁵

C. pneumoniae is transmitted in ways similar to the common cold, though not as easily. It’s spread often and to people of all ages. Infection frequently produces no symptoms, but it may cause mild sore throat or sinus problems, or a more severe, prolonged cough, which is generally diagnosed as bronchitis or pneumonia. The infection may persist for a long time. Very recent infection can be diagnosed with antibody testing, but the testing isn’t readily available. Even where it is available, it’s underutilized.

IgM and IgG:

Antibodies are proteins produced by the immune system that latch on to invading bacteria and viruses and help to kill them. A particular kind of antibody called IgM is generally found only during a first infection by any bacteria or virus, and it can thus be used as proof of a very recent infection. Chronic infection, i.e., infection that started more than a few months earlier, is harder to diagnose, because the IgM disappears quickly.

The kinds of antibodies that the body produces next, called IgG, can linger for years after the infection has disappeared. In other words, IgG antibodies could mean that an infection persists, but they could also mean that there was an infection in the past that is no longer present. No wonder, then, that this common infection is hard to diagnose.

Because I happened to see Susan near the beginning of her illness, she still had IgM antibodies against C. pneumoniae. Later, the IgM disappeared, and she then developed high levels of IgG antibodies that lasted for many years, even after she was treated.

One of the unique aspects of Chlamydia is that it must live and reproduce inside cells. Most of us humans worldwide have been infected at one time or another with C. pneumoniae. But Chlamydia tries to stay off of our immune systems’ radar screens, unobtrusively hunkering down. Many of us live in peaceful co-existence with C. pneumoniae, remaining alive and well. But some of us remain alive and unwell. In the process of responding to this uninvited guest, our immune systems can sometimes become irritated and overreact, which can do damage to our tissues and cause inflammatory diseases—like asthma.

* Some scientists refer to these bacteria as "Chlamydophila instead of Chlamydia. But a majority of scientists who study these bugs prefer Chlamydia," so that is the term I will use throughout this book.

I suggested that Susan try three weeks of treatment with doxycycline, a tetracycline antibiotic recommended for treating acute C. pneumoniae infections.⁶ She readily agreed. After that, I became busy with my other patients, and I didn’t spend a lot of time thinking of Susan until about a month later, when she called to ask for a refill of doxycycline. When I asked her why she thought she needed more antibiotics, she told me that her wheezing had gone away after she started on the doxycycline. After she’d finished it, the wheezing had started to come back. Intrigued, I prescribed two more weeks of treatment. Susan completed the treatment—and remained completely asthma-free for the next two years.

Medical scientists argue that clinical stories, including case reports like Susan’s, are the weakest form of scientific evidence and can be misleading. And I agree. But never underestimate the power of a single compelling story to motivate a research career.

Why Did I Write This Book?

The simple answer is because there is a new treatment for asthma that your doctor probably has not discussed with you. It’s my hope that those suffering from asthma symptoms might benefit from this new treatment now.

The complicated answer is because more research is needed before the full future benefits of this new treatment will be completely understood, and I’d like to help move the research forward. In section two, I summarize the scientific evidence behind the treatment to show that there is more than sufficient evidence to support definitive research. And if the research turns out to work as I predict, the results might influence asthma guideline recommendations and make this treatment more widely available.

Because there’s not yet enough evidence-based research on C. pneumoniae’s possible links to asthma, I’ve included several case studies like Susan’s that demonstrate the real, human toll difficult-to-treat asthma can take on quality of life and the remarkable benefits that antibiotic treatment can have on the lives of some asthma sufferers who try it. And since this is a book about stories—not just patients’, but also asthma experts’—I’ll start with my own to explain how I came to discover this novel treatment.

I began medical school at Stanford in the late sixties with the ambition of becoming a medical researcher in the traditional mold. But along the way, I became a family physician instead. What happened?

When I started medical school, the watch-phrase was clinical relevance! Researchers were interested in which facts were important for patient care—but the kind of patient care research being conducted at large academic medical institutions like Stanford did not necessarily always translate into patient care in the real world. In leaving academia to become a family physician, my goal was to identify which medical issues people struggled with in their everyday lives and research those. I didn’t realize at the time how unusual it was to become a primary care doctor who maintained an interest in research.

My career choice had its costs. Because there was virtually no medical research conducted outside of academia, I had no institutional infrastructure and limited funding to support my research. But my career choice has also had its benefits. I have had more intellectual freedom than many professional academic researchers. When I encounter a medical problem in the course of my practice and interactions with patients, I can research it without external pressures or incentives. In contrast, professional academic medical researchers are frequently constrained by available grant funding, and are compelled to publish or perish. As a result, they sometimes choose conventional rather than controversial topics. In some cases, academics’ research also suffers from limited access to real world patients. And occasionally, researchers may also be swayed by financial ties to funding organizations, though of course there are also many academic researchers doing vital, innovative research. Over the years, I have been fortunate enough to collaborate with many who have been willing to lend generous intellectual and moral support.

Towards a Cure

I began my journey towards Jim Quinlan’s asthma cure in medical school in the late sixties and early seventies. Initially, it was slow going: in medical school, I was trained not to prescribe antibiotics for viral (i.e., non-bacterial) respiratory illnesses such as the common cold. But as soon as I entered practice in Madison, Wisconsin, my training confronted reality. Two of the older physicians in my practice routinely gave shots of penicillin to their patients infected with viral-like respiratory illness symptoms. Those patients demanded penicillin shots from me, too. Being a modern, recently trained physician, I declined to use penicillin. But I did agree to prescribe an antibiotic: erythromycin.⁷ As a consequence of this grand compromise, I began encountering a few patients with persisting respiratory illnesses who appeared to improve after taking erythromycin but got worse again after stopping it. Re-treatment often cured them of their symptoms. So I began to wonder if the cause of their illnesses was bacterial after all—and if I could find it lurking somewhere.

Fast-forward to the mid eighties, when Dr. Tom Grayston and his colleagues at the University of Washington in Seattle reported the discovery of a new respiratory bacterium capable of causing sore throats, coughs, and pneumonia (see Chlamydia Pneumoniae ).² The treatment for this newly described bacterium, now called Chlamydia pneumoniae, included erythromycin; re-treatment or prolonged treatment was often needed for success, they wrote.⁶

Dr. Grayston’s group was the first to report respiratory illness caused by C. pneumoniae in the U.S. I decided to see if their research applied in Wisconsin. I contacted the Wisconsin State Laboratory of Hygiene and eventually collaborated with immunologist Dr. Rik Golubjatnikov and his laboratory technician Ruth Dodge. A dozen of my primary care practice partners and I collectively enrolled 365 patients with acute respiratory illnesses into what we called the cough study. We then published our findings in the Journal of the American Medical Association (JAMA) in 1991.⁸ The cough study was an early example of practice-based primary care research, which is becoming increasingly popular in the U.S. (For more on practice-based research, see Chapter 13.)

Our JAMA report confirmed the Seattle findings that C. pneumoniae infection caused 5 percent of acute bronchitis and 20 percent of community-acquired pneumonia. (Acute bronchitis is the medical term for what is often called a chest cold, with coughing. And community-acquired pneumonia is distinct from the hospital-acquired variety that can be more severe and difficult to treat.) But the bronchitis and pneumonia results paled in comparison to a serendipitous discovery that became the main focus of the JAMA article: C. pneumoniae infection was associated with wheezing, asthmatic bronchitis and adult-onset asthma. We speculated that the association we found was causal, and suggested that C. pneumoniae might be a treatable cause for asthma. We also ventured to propose that early treatment might even prevent the development of asthma.

The JAMA article was reprinted in several international editions. A local TV station interviewed me in my office, and the interview was rebroadcast worldwide by CNN. After it aired, the palace physician in Amman, Jordan, reached out to me through a Jordanian-born oncologist at the Medical College of Wisconsin. He was the personal physician for King Hussein’s brother, who suffered from severe, steroid-dependent asthma. (I relayed my limited clinical experience but never heard the outcome.)

I was also contacted by Pfizer, Inc., which was interested in supporting a study using their newly approved macrolide antibiotic, azithromycin. Azithromycin seemed like it might be a very promising treatment against Chlamydia: it’s unique among macrolide antibiotics in that it prefers to accumulate inside cells where the Chlamydia hang out. Most other antibiotics freely leave the intracellular environment after a person stops taking a dose but azithromycin cannot exit and so very