Case Report: COPD and Anxiety Resolved by Integrative Medicine

by Jeremy Mikolai, ND, and Martin Milner, ND

Introduction

Chronic obstructive pulmonary disease (COPD) is a condition characterized by chronic airway inflammation leading to an objective decline in ventilatory function. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), a report produced by the National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO), defines COPD as “ … airflow limitation that is not fully reversible … usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.”¹

COPD is the third leading cause of death in the US, claiming more than 137,000 lives annually.² It is a significant contributor to decreased quality of life and to deaths from pulmonary infections such as pneumonia and influenza, and it is frequently accompanied by comorbid conditions including coronary heart disease. COPD is a large and important contributor to our national annual health-care burden and, in the vast majority of cases, is completely preventable.^1–5

Three antecedent conditions generally lead to COPD: emphysema, chronic bronchitis, and asthma. These conditions may be present alone or in combination and often occur in series. Any of the three conditions can exist in a patient with or without COPD.² Emphysema (EM), chronic bronchitis, (CB), and asthma (AS) have distinct pathophysiologies, yet these are all essentially inflammatory airway diseases and therefore have the potential to result in chronic airway obstruction. Other important causes of COPD exist (such as cystic fibrosis, alpha 1-antitrypsin deficiency, and others), but are far less common.

The three conditions, EM, CB, and AS, each begin by affecting a different part of the lungs preferentially. Once COPD manifests, the airways themselves become resistant to the flow of air into and out of the lungs. That resistance, or “obstruction,” characterizes COPD regardless of the condition that causes it. In all but rare instances, exposure to inhaled irritants, particularly tobacco smoke, is the primary risk factor for developing the inflammatory changes that lead to airway obstruction. It is estimated that nearly all smokers develop some degree of airway obstruction despite the fact that only a fraction of these are diagnosed.^6–9

Reversibility is an important aspect of COPD. By reversibility, we mean that a portion of the obstruction can be improved by intervention or spontaneous remission. Initially, any of the three conditions EM, CB, or AS can be largely reversible, but as any of the diseases progress in severity or duration, the rule is that the obstructive deficit becomes less reversible.^1,2,10

Pulmonary function tests (PFTs) are the measure by which we quantify the ability of the lungs to exchange gases and ventilate air. Many pulmonary function tests exist and range from a simple measure of airspeed to the amount of gases dissolved in the blood. Spirometry is the standard set of PFTs by which we diagnosis airway obstruction. Spirometry is available in many primary care offices and in the office of every pulmonologist. The exact parameters included in the test can vary somewhat from instrument to instrument; but three parameters, FVC, FEV1, and FVC/FEV1, are universal, and two others, FEF25-75 and maximum flow, are included in most cases.

The FVC (forced vital capacity) is the amount of air (in liters) that can be expired after a maximal inspiration. The FEV1 (forced expiratory volume in 1 second) is the maximum volume of air (in liters) that a person can expire during the first second after a maximum inspiration. We divide the FEV1 by the FVC to give us the ratio between the two (FEV1/FVC).

The FEF25-75 (forced expiratory flow between 25% and 75%) is the speed (in liters per second) at which a person can empty the middle half of her air during a maximum expiration. The FEF25-75 is typically the earliest parameter to change in obstructive lung disease. The maximum flow is the maximum airspeed (in liters per second) that a person can generate during maximal expiration. This measure is the same as the peak expiratory flow (PEF, or “peak flow”) that most providers use in office to monitor asthma, except that PEF is often expressed in liters per minute.¹¹

We compare the spirometry values generated by a patient to predicted values. Predicted values are based on our expectations of an average patient, in good health, of the same gender, age, and height (therefore, with a lung size that is assumed to be the same). When we talk about the results of spirometry, we talk about the patient’s values compared with the expected or percent of predicted value (%pred).

The hallmark changes seen in obstructive lung disease are decreases in rapid, early airflow. The average healthy person should be able to empty more than 70% of her FVC in the first second of maximum expiration. Therefore, the diagnosis of COPD depends upon an FEV1/FVC ratio equal to 0.7 or less. The average healthy person should be able to expire 80% or more of her predicted FEV1 in the first second of maximum expiration. Therefore the diagnosis of COPD also requires that the FEV1 %pred be less than 80%.^2,12

We said that the FEF25-75 is usually the first parameter to change in obstructive lung disease. It is abnormal for the FEF25-75 to be lower than 60%pred, but this parameter is not diagnostic and has relatively poor reproducibility. The DLCO is the diffusion capacity of carbon monoxide across the respiratory epithelium. The RV is the residual volume of air left in the lungs after full expiration. The DLCO becomes abnormally low in COPD, whereas the RV becomes abnormally high.¹³

We often perform PFTs before and after the administration of a bronchodilator medication. We call this a pre-/postmedication challenge (PPM). The PPM can be used to assess effectiveness of bronchodilator therapy, to document the amount of reversibility present in the disease, and to stage the disease.¹²

Case Report

C. N. , a 23-year-old male, reported to a local hospital in Georgia with complaints of chest tightness, dyspnea on exertion, dizziness, and tingling sensations in his upper limbs. He underwent evaluation and testing, including urine and blood chemistries, creatine kinase, myoglobin, viral serologies, pre-/postmedication pulmonary function tests (Table 1), and chest radiography (CXR). His CXR was normal and his lung function was considered to demonstrate mild fixed COPD without significant reversibility. The patient was placed on bronchodilator therapy: inhaled albuterol 90 mcg/spray MDI, 2 puffs every 4 to 6 hours as needed.

TABLE 1 HERE

C. N. left Georgia and returned to his mother’s home in Texas. The following month he reported to a local hospital to complete further testing. He reported a tobacco smoking history of approximately one pack-year, but a nearly 10-year history of daily marijuana smoking. He also reported that there was heavy indoor smoking in the home while he was growing up. Pulmonary function tests (PFTs) were repeated and revealed normal arterial blood gases (ABGs) and predominantly normal pre-/postmedication spirometry testing (PPM), with severely depressed diffusion tests (DCLO; Table 1). An extensive laboratory investigation for secondary causes of COPD was completed; all results were within normal limits.

The patient and his family relocated to Portland, Oregon, in early 2009. In autumn 2009, he completed a screening study for sleep apnea that revealed nonspecific findings suspicious for disordered breathing. This result prompted a recommendation for a follow-up overnight sleep study, which was never completed.

In early 2011, the patient presented to a community clinic of the National College of Natural Medicine (NCNM) in Portland with complaints of anxiety, shortness of breath (SOB), and lightheadedness. He reported chest tightness with activity and frequent episodes of panic. His medication use at that time included 0.5 to 1.0 mg/day of alprazolam and 10 mg/day paroxetine (both for anxiety), and albuterol 90 mcg/spray MDI, 2 puffs as needed.

C. N. was referred to us at the Center for Natural Medicine’s Heart & Lung Wellness program for evaluation of his pulmonary complaints. His PFTs at that time revealed no diagnostic changes; his FEF25-75 was abnormally low, as was his maximum flow (PEF; Table 1). His resting oxygen saturation by pulse oximetry was normal at 99%; however, a 3-minute ambulatory pulse oximetry challenge revealed that his oxygen saturation became depressed to 93% during minimal exertion.

Over the next several weeks, further history and physical examination data were collected and an initial treatment plan implemented. The history revealed that he felt winded with minimal activity, especially push-ups and weight lifting, and had feelings of presyncope with exertion. C. N. revealed that he was feeling “at the breaking point” regarding his stress level, which he rated 10/10 (10 worst). He thought that he was responsible for supporting many people and was reticent to “burden others with his problems.” His physical examination was normal across 10 systems, including normal chest expansion, symmetry, and diameter. He had recently self-initiated an increase in his use of alprazolam to 2 mg/day and a discontinuation of paroxetine.

The initial treatment plan included the use of nebulized albuterol 2.5 mg/3 mL every morning, homeopathic phosphorus 6C, twice daily; 3 to 6 grams orally of vitamin C/day, nightly Epsom salt baths, and a recommendation to end his showers with cold water. We emphasized the importance of deep breathing exercises and instructed C. N. to begin counting the lengths of his breaths making sure that the duration of his exhale was longer by at least two counts than his inhale, to exhale through pursed lips for several minutes several times daily, and to breathe from his belly, like trying to raise a rock with his breath. He was advised to find a river rock and set it on his abdomen for a few minutes every day while lying supine to help him get the sensation of belly breathing and to help him feel grounded.

Over the next several weeks, the patient experienced an increase in his anxiety. A homeopathic preparation of alprazolam 6C daily, 20 mg/day of fluoxetine, and 4 cups/day of a tea formulation of chamomile, hops, catnip, skullcap, yarrow, and peppermint, were added to the plan over subsequent visits.

Over the two week period following the addition of fluoxetine to the treatment, the patient complained of side effects including hot flashes, drowsiness and yawning, fatigue such that he could fall asleep at the wheel, occasional muscle spasms, lightheadedness, shaking, tremor, and nausea. He attributed these all to fluoxetine; all of them abated after discontinuing it. We switched to paroxetine 10 mg/day, which he had previously tolerated, and prescribed a slow and controlled down titration of his use of alprazolam. His primary homeopathic remedy was changed to Arsenicum album 6C three times daily.

After three months of treatment with minimal symptomatic improvement, the PPM tests were repeated and demonstrated no improvement in lung function and a decline in several parameters (Table 1). The patient had also begun complaining of tingling and numbness in both hands, so examinations for musculoskeletal dysfunction and treatment with manual and physical medicine modalities were undertaken. We tested C. N. ’s alpha 1-antitrypsin (A1AT) level to rule out deficiency as a cause of his COPD. The A1AT level had not been measured in initial evaluations from 2008, but his 2011 result was normal. We discontinued the patient’s daily nebulized albuterol due to the lack of improvement in lung function, but the rest of the treatment plan was continued.

By early summer, the patient began to report that he was waking from sleep “feeling really good.” He reported that his mother also noticed a difference in his attitude and that he had not had any “severe spells” of dyspnea for several months. He had been able to titrate down to 1 mg/d of alprazolam use. He also reported having successfully cut down on his marijuana use. We initiated more soft tissue musculoskeletal treatment and increased the potency of Arsenicum album to a single dose of 12C pellets daily.

Over the next several weeks, C. N. was able to titrate down to 0.75 mg/d of alprazolam. He was increasingly able to deal with his anxiety through reframing and control of his breathing. We added daily thoracic castor oil packs to his regimen and replaced the peppermint in his tea formulation with Tilia tomentosa.

C. N. continued to successfully titrate down his alprazolam use over the subsequent weeks. As he did so, he reported feeling more agitation, a “shorter fuse”; he found himself stricter with his son, lacking focus during daily tasks, and feeling more sensitive/intolerant to the presence of other people. He had one panic attack while lying in bed insomnious. The event occurred between 2 and 3 a.m., and C. N. proudly recounted how he was able to “to pull himself out of it” using prayer, breathing, and reframing. We added a flower essence to his daily regimen: equal parts garlic, cayenne, St. John’s wort, self-heal, and mimulus, to be used a few drops at a time as needed.

The following week, C. N. took his final dose of alprazolam. We increased his paroxetine dose to 20 mg/d. He reported two instances of nosebleeds and two migraine headaches, which prompted us to switch his homeopathic remedy back to phosphorus at a higher potency of 12C once daily. We also added a botanical nervine tincture composed of hops, oat, and lemon balm (equal parts), to be used a few milliliters at a time as needed, and a lobelia rescue tincture composed of Lobelia inflata (1 part), Capsicum annuum (0.5 parts), and 3X homeopathic ephedra (2 parts), with instructions to take 1 mL every 15 to 30 minutes as needed for sensations of SOB.

In mid-August 2011, the patient was reevaluated using PPM spirometry. In this instance, the lobelia rescue tincture was used as the bronchodilator medication rather than albuterol. In the premedication test, the patient demonstrated his personal best FVC and FEV1. His FEF25-75 was his second best ever, was within normal range, and was improved by 0.89 L/second over his previous test. His PEF improved by 0.99 L/second (13% change) after administration of the lobelia rescue tincture, resulting in his personal best and first recorded normal PEF (over 80%pred.; Tables 1 and 2).

TABLE 2 HERE

In the following weeks the patient reported feeling “well and excited” and that he was “just sitting back and letting it happen” when feeling lightheaded or anxious. He reported that anxious feelings were happening less frequently and that he could work through them with breathing when they did occur. He reported feeling physically down when he did not take his homeopathic phosphorus.

Our final follow-up visit with C. N. was in December 2011 for a paroxetine refill. He reported feeling much better with no big attacks of dyspnea, SOB, cough, or hyperventilation and no panic attacks since last visit. His elevated hematocrit had returned to normal and this potentially supported his feelings that his breathing difficulties during sleep had resolved. We have not seen him in 2012.

Discussion

COPD was almost certainly overdiagnosed in C. N. ’s initial evaluation by the pulmonologist in Georgia. C. N. never met the most basic criteria for COPD diagnosis by PFTs; his FEV1/FVC ratio was never less than 0.7 and his FEV1 was never below 80%. Moreover, spirometry tests are prone to error, and false positive tests are common. Substantial coaching and instruction are necessary to achieve adequate results. Studies have demonstrated that adherence to American Thoracic Society (ATS) quality-control standards for PFTs are less than 80%, even in offices where the tests are routinely performed.¹⁴ There was an abnormal DLCO test suggestive of COPD in October 2008, but the evaluating physician noted that the value was “questionable.” Ideally, the DLCO would have been reevaluated after the August 2011 PFTs; it was not.

The increased reversibility of C. N. ’s airway obstruction is one of the greatest successes in this case. Our first PPM confirmed the original assessment that only minimal reversibility was present. The final PPM test demonstrated an increase of 0.99 L/sec, or 13%, in PEF. The change in his pre- and postmedication FEF25-75 during the final test was 16%, and the improvement in postmedication FEF25-75 over his September 2008 value was 17%; all of these are substantial improvements in reversibility (Table 2). The best measure of reversibility is the FEV1. C. N. ’s final pre- and postmedication FEV1s were each improved by 7% over his initial test in September 2008. However, because his FEV1 was never lower than 80%, the significance of this change is difficult to quantify.

The bronchodilator used in the final PPM test is a novel botanical formula that we have used for many years. We have had immediate in-office improvements with its use and many anecdotal accounts of its effectiveness. There are demonstrable physiologic effects in the medical literature for each agent in this formula, which support the plausibility of its therapeutic potential. Lobeline and beta-amyrin palmitate from lobelia increase norepinephrine (NE) release and inhibit dopamine (DP) uptake.^15,16 Lobeline can increase inspiratory and expiratory flow rates.¹⁷ The effect of capsaicin on small diameter afferent pulmonary fibers has been demonstrated.¹⁸ The alpha- and beta-adrenergic stimulation of crude dose ephedra is well known. Adverse events related to those effects resulted in its removal from the American market by the FDA in 2004.¹⁹ Bronchodilator effects from the homeopathic preparation of ephedra, especially at lower potencies, are therefore plausible. We believe that this formula warrants further deliberate investigation.

The importance of breathing exercises and rehabilitation of dysfunctional breathing patterns in the success of this case cannot be overstated. The patient’s symptoms were likely more attributable to dysfunctional breathing than mild COPD. We expect this based on his sleep screening study from 2009, which assessed dysfunctional breathing patterns, the fact that he suffers from anxiety and panic, and the fact that his symptoms overlap well with the constellation often seen in the so-called hyperventilation syndrome.²⁰

A final success in this case was the titration of the patient off of benzodiazepine anxiolytic therapy. The down titration of benzodiazepines after prolonged daily use must be slow and controlled.^21–23 This case demonstrates that, with appropriate titration schedules and supportive treatments, discontinuation of long-term benzodiazepine use can be successful in the integrative outpatient setting. For anxiety, in general, the success of the naturopathic mixed methods approach to treatment is further supported by controlled trial evidence in the medical literature.²⁴

This case also demonstrates one of the greatest difficulties in studying integrative medicine: we cannot know which treatment is responsible for the patient’s improvement. Integrative medicine uses mixed methods; we almost never implement a single treatment for a single condition. While this is a weakness that pervades our attempts to research our methods, it is also a strength: individualized treatment. It will remain our challenge to find ways to scrutinize the medicine that we practice, to measure and document its successes and failures, and to do so without reducing it to merely the sum of its parts.^25–29

Acknowledgments

The authors would like to acknowledge the four naturopathic physicians who contributed significantly to the management and success of this case while they were interns in the Heart & Lung Wellness program: Carolyn Jones, ND; Emily Dickmeyer, ND; Jennifer Elton, ND; and Lacey Kidd, ND.

To contact the authors or for further information:

Dr. Martin Milner & Dr. Jeremy Mikolai

Heart and Lung Wellness Program

Center for Natural Medicine Inc. (CNM)

1330 SE Cesar E Chavez Blvd.

Portland, Oregon 97214

503-232-1100, ext. 303

CNMWellness.com

HLResident@cnmwellness.com

These authors have no financial conflicts of interest to declare.

Jeremy Mikolai, ND, is in his third year as the Heart & Lung resident under the mentorship of Dr. Martin Milner, at the Center for Natural Medicine (CNM) Heart & Lung Wellness program and is the chief resident at the National College of Natural Medicine (NCNM), both in Portland, Oregon. Dr. Mikolai is active in research and is an adjunct faculty member in the Masters of Science in Integrative Medicine Research (MSiMR) program at the Helfgott Research Institute at NCNM. He is actively working to create the first ND clinical fellowship in cardiology.

Martin Milner, ND, has been in private practice since 1983 and is the medical director of the Center for Natural Medicine Inc. CNM functions both as an integrated group medical practice and as a teaching clinic of NCNM. CNM is also active in clinical trials and research. Dr. Milner is the professor of cardiovascular and pulmonary medicine at NCNM and has been since 1986. He continues to supervise and mentor 48 ND student interns per year in the Heart & Lung Wellness Program, which he has maintained since 1999. He trains two ND residents each year, one who assists him in the Heart & Lung Wellness program and one in his private practice. Dr. Milner is actively pursuing, with Dr. Mikolai, the creation of the first board certification program for NDs in naturopathic cardiology.

Notes

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