Interview with Dr. Purvi Parikh and Dr. Paul Ehrlich
“The study of asthma is the study of one patient” Dr. Anthony Gagliardi
Readers of Asthma Allergies Children: a parent’s guide may recall this adage, which Dr. Ehrlich is fond of quoting, referring to the fact that “asthma” is not one disease but a set of symptoms from disparate sources, and thus may not respond to familiar treatments. One cornerstone of treatment for those who experience severe exacerbations is to respond to “yellow zone” peak flows (zone 2 in the UK) by stepping up doses of inhaled corticosteroids (ICS) by multiples of 4 or 5 to stave off hospitalization and doses of oral steroids. In analyzing two new studies of this tactic, a recent editorial in the New England Journal of Medicine by Philip G. Bardin, F.R.A.C.P., Ph.D. suggests that another bit of conventional wisdom should be retired.
One study looked at children ages 5 to 11 with mild-to-moderate persistent asthma, all of whom all of whom had suffered at least one exacerbation in the previous year who were receiving low-dose ICS. Dr. Bardin concludes, “Overall, this commendable trial indicates that escalating the dose of inhaled glucocorticoids is a failed strategy to prevent exacerbations in children with early symptoms of asthma instability.” The second trial, done in the UK, involved adults and adolescents. While the methodologies were different, Bardin says, “Evidence indicates that substantial escalation of regularly used inhaled glucocorticoids, even by a factor of 4 or 5, fails to prevent most asthma exacerbations.” Add to this concerns about the safety of ICS that have emerged over time and we have problems.
What to make of this? How will allergists address this new thinking with their patients? I turned as I often do to my cousin and to Dr. Parikh, with whom he practices. – Henry Ehrlich
AAC: Purvi and Paul—thanks for taking time to help sort out this new data. Paul, I’d like to ask you the first question. You have been in practice for longer. Can you give us a feeling for how standard of care has evolved for this kind of asthma presentation over the years? And Purvi, as someone who trained much more recently than Paul (sorry Paul) could you describe how this subject was addressed in your fellowship?
Paul: Your question made me think back to my days as a house officer at Bellevue Hospital in the early 70’s. We saw many asthmatics dealing with a huge, poorer population in New York City when acute treatment consisted of theophylline given intravenously, IV fluids, oxygen and LOTS OF STEROIDS. As my good friend and former teacher Arnold Levinson said a few years ago at a meeting with the The New York Allergy & Asthma Society, things have moved slowly ever since the discovery of IgE by the Ishizakas—Japanese researchers whom I met at Johns Hopkins when I was at Walter Reed Army Medical Center. The use of theophylline has all but disappeared, and we still rely on corticosteroids. It is only in the past five years that we have added newer modes of care, but corticosteroids are still prominent.
Purvi: During my fellowship, standard of care was evolving before my eyes. There was a push for using steroid-sparing agents such as Xolair (omalizumab). I trained at an institution that was doing clinical trials with the new monoclonal antibodies. Also, anticholinergic inhalers (tiotropium; brand name Spiriva), used for decreasing steroid use for COPD, were also effective with asthma so we incorporated them in treatment.
AAC: Purvi, you said when we talked recently that this subject was discussed at the recent meeting of the American Academy of Allergy, Asthma, & Immunology. Can you summarize for our readers the general tone of those discussions?
Purvi: There was a real buzz because now there are so many new treatment modalities on the horizon that target various parts of the immune system. This is exciting because we can provide better, personalized care for our patients and get many off toxic steroid doses. There was especially a lot of promise in those steroid-resistant asthmatics who may not be allergic but still suffer quite a bit. Some of these new modalities help control their asthma quite well. Also, we are learning what tests and biomarkers will help us identify the right drug for the right patient.
AAC: Paul, you are the one who returns continually to your friend Dr. Gagliardi’s adage that the study of asthma is the study of one patient. That has been borne out over the years by the continual identification of new asthmatic phenotypes—i.e. the symptoms may look like classic allergic asthma but closer observation shows that this is not the case. The Bardin editorial points to asthma “linked to provocative factors such as viral or bacterial infections, nonadherence to treatment, allergen exposure, and environmental air pollution.” How do you tell the difference in your practice and how does it translate into asthma action plans for your patients?
Paul: That is a great question, and Dr. Parikh and I can answer that very easily. I think of Dr. Gagliardi’s comment often which stated that each case is different, and, therefore, a complete history is crucial in formulating of appropriate treatment. When does the asthma get worse? When and where is it not a problem? When we get a referral from a non-specialist we look at the medication history to see what has worked and what has not. The side effects from each medicine and so forth.
AAC: Purvi, we have seen tremendous strides in developing new biologics for asthma and other atopic diseases—the IL-5 inhibitor mepolizumab (NUCALA) comes to mind. To your knowledge what is the record of these new drugs in staving off exacerbations?
Purvi: In addition to mepolizumab, we have also seen promise with benralizumab (IL-5 receptor antagonist) that is also approved. I am excited to see what will come from studies with dupilumab (IL-4Ra) and asthma as it has already worked wonders for patients with atopic dermatitis. These new drugs appear to be helpful in avoiding exacerbations in either patients who have failed other agents such as omalizumab or a particular set of eosinophilic asthmatics who may not all be allergic/atopic. We are learning the eosinophil plays a role in NON-allergic asthmatics as well from these studies with anti-IL-5 agents. These drugs are expensive, but insurers have seen the benefits that should translate into less emergency treatment that will save money in the long run.
AAC: This is addressed to both of you. Whenever a deeply ingrained clinical approach is challenged, the question becomes how to cope in the short run. Some of our readers may be accustomed to upping their doses as described in the studies. What should they do? What should they say to their doctors? And what should their doctors say to them? (If you could just give say three takeaways for patients and doctors that would be useful.)
Purvi: Well, if you are needing even one course of oral or injectable steroid in a year whether from an ER, urgent care, or doctor you need to have a conversation with your doctor about other agents as just one exacerbation is considered uncontrolled. The same goes for nighttime symptoms, frequent rescue inhaler use, trouble with household chores etc. If your doctor keeps increasing the steroid dose in the inhaler itself, and you do not see much difference in your control you should see your doctor or an asthma or allergy specialist to see if there are better options out there for you. You may be one of these “Steroid resistant asthmatics” Asthma is not a one size fits all diagnosis.
Paul: For many years, before and after Purvi and I began to practice together, I rarely had an asthma patient require emergency treatment. For allergic patients this usually involved better housekeeping and otherwise avoiding triggers as well as diligent peakflow metering and other good habit, as well as conscientious medication use. But I also saw a lot of stress-induced asthma (that’s a big one in New York City, occupational asthma, exercise-induced asthma, viral-induced asthma, and so forth that had little to do with allergic asthma. They will not be helped by these wonderful new treatments that Purvi has described. So patients and doctors still have to play detective and arrive at the behavioral modification that can ameliorate those symptoms.
AAC: Thank you both for your time. Now get back to your patients.
Dr. Purvi Parikh is an adult and pediatric allergist and immunologist. She completed her fellowship training in allergy and immunology at Albert Einstein College of Medicine’s Montefiore medical center following her residency at the Cleveland Clinic and is board certified by the American Board Allergy and Immunology, as well as the American Board of Internal Medicine. Dr. Parikh has published articles on allergy, asthma and immunodeficiency syndromes in the Annals of Allergy, Asthma and Immunology, The Journal of Gastrointestinal Cancer and is currently writing a chapter for an otorhinolaryngology textbook. Dr. Parikh has also presented research at various national and international meetings. She is passionate about health policy and sits on the health and public policy committee for the American College of Physicians. She also is a board member and founder of the Share and Care Foundation’s young professional committee, which raises money for underprivileged women and children in India.
Dr. Paul Ehrlich is an author of Asthma Allergies Children: a parent’s guide and co-founder of this website. He works with Dr. Parikh at Asthma & Allergy Associates of Murray Hill in New York City.