What Matters More?

The doctor’s…or the patient’s perception of their treatment?  Interesting question!  Even more interesting, it is one that was posed in an editorial in the current edition of the New England Journal of Medicine.

The question arose after a new study showed that patients’ self-assessed outcomes in clinical trials can mask a real lack of an objective effect. The accompanying editorial took a completely different stance – asking, “What is the more important outcome in medicine: the objective or the subjective, the doctor’s or the patient’s perception?”

The double-blind, crossover study in question was led by Michael Wechsler, MD, an SRxA Advisor.  It set out to determine whether responses to placebo differ from the physiological changes that occur without any intervention in patients with asthma. To address this, they compared the effects of an albuterol inhaler, two placebo interventions (an inert inhaler and sham acupuncture needle) versus “no treatment” in which patients were told to wait for several hours and then return home.

46 patients with stable asthma underwent each of four treatments over a series of visits. At each visit, lung function was measured by spirometry every 20 minutes for 2 hours.  Also at each visit, patients were asked to score any perceived improvements in asthma symptoms on a visual-analogue scale with scores ranging from 0 (no improvement) to 10 (complete improvement). Patients were also asked whether they thought they had received a genuine therapy or placebo.

Among the 39 patients who completed the study, improvement in maximum forced expiratory volume in 1 second (FEV₁) was significant only after albuterol, however albuterol provided no incremental benefit with respect to the self-reported outcomes.

In other words… from the patients’ perspective all the interventions, except waiting, worked.

While the authors acknowledged that placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma, they argued that from a clinical-management and research-design perspective, patient self-reports can be unreliable.  They concluded: “Objective outcomes should be more heavily relied on for optimal asthma care.”

However an accompanying editorial in the same journal questions the authors interpretation.

In it, Daniel Moerman, Ph.D. asks: “Are patients wrong if they report improvement even if there is no evidence for this?” He argues that it is after all subjective symptoms such as wheezing, rather than reduced FEV1 that brings patients to seek medical attention in the first place.

Hence the question, What is the more important outcome in medicine: The objective or the subjective, the doctor’s or the patient’s perception?

All medical procedures whether active or placebo, he argues, are meaningful insofar that they represent something. These meanings create expectations that can dramatically modify the effectiveness of even the most powerful proven treatments. He gives an example of a recent experiment that showed the effects of an opioid drug were either doubled or extinguished by manipulating subject expectations and that  MRI scans showed brain mechanisms differed as a function of these expectations.

Moerman asks: “Do we need to control for all meaning in order to show that a treatment is specifically effective?” Maybe, he suggests, it is sufficient simply to show that a treatment yields significant improvement for the patients, has reasonable cost, and has no negative effects.

What do you think? Is perception reality?  We’d love to know.

An apple with your albuterol?

According to a study presented at the recent American Thoracic Society, people with asthma may be well-advised to avoid heavy, high-fat meals.

Individuals with asthma who consumed a high-fat meal showed increased airway inflammation just hours after the binge.  The high fat meal also appeared to inhibit the response to the asthma reliever medication albuterol.

“Subjects who had consumed the high-fat meal had an increase in airway neutrophils and TLR4 mRNA gene expression from sputum cells, that didn’t occur following the low fat meal,” said research fellow Dr. Lisa Wood, Ph.D. “The high fat meal impaired the asthmatic response to albuterol. In subjects who had consumed a high fat meal, the post-albuterol improvement in lung function at three and four hours was suppressed.”

Researchers recruited 40 asthmatic subjects who were randomized to receive either a high-fat, high-calorie “food challenge”, consisting of burgers and hash browns containing about 1,000 calories, 52% of which were from fat; or a low-fat, low-calorie meal consisting of reduced fat yogurt, containing about 200 calories, and 13% fat.

Sputum samples were collected before the meal and four hours afterward, and analyzed for inflammatory markers.

Subjects who had consumed the high-fat meal had a marked increase in airway neutrophils and TLR4 mRNA gene expression. TLR4 is a cell surface receptor that is activated by nutritional fatty acids: TLR4 ‘senses’ the presence of saturated fatty acids, and prompts the cell to respond to the fatty acids as if they were an invading pathogen, releasing inflammatory mediators. Subjects who had consumed the high fat meal also had reduced bronchodilator response.

The mechanism by which a high fat meal could change the bronchodilator response requires further investigation.  However if these results are confirmed by further research, strategies aimed at reducing dietary fat intake may be useful in the overall management of asthma.