Danger of Reliance on Placebo Effect

With asthma patients, giving an inhaled bronchodilator medication, like albuterol, can result in a rapid improvement in airflow that can be objectively measured using spirometry testing. This testing can be repeated over a short period of time, thus making asthma an excellent model for assessing a “placebo effect” (benefit resulting from simulated treatment or the experience of care).

In a randomized, double-blind, cross-over study published in the New England Journal of Medicine, Wechsler et al compared 4 intervention arms in asthmatic patients:

  1. Active medication—double-blinded albuterol inhaler
  2. Placebo #1—double-blinded inert inhaler
  3. Placebo #2—single-blinded sham acupuncture
  4. No intervention at all

Only those asthmatics with documented FEV1 bronchodilator responsiveness (of at least 12%) were enrolled and each study subject received each of the four interventions three times.

The authors looked at objective evidence of airflow improvement by measuring spirometry, as well as self-reported subjective improvement, and here is what they found:

  1. Albuterol produced a significant improvement in FEV1 (20.1%), as compared to only about 7% with each of the other three interventions (p<0.001). There was no statistical difference in airflow improvement among either placebo arm or the “nothing” arm.
  2. Patients’ subjective report of improvement did not significantly differ between the albuterol inhaler (50%), placebo inhaler (45%), or sham acupuncture (46%), but all three were significantly better than no intervention (21%)(p<0.001).
  3. In an assessment of treatment credibility (percent of subjects’ subjective belief they had received an active treatment), sham acupuncture (85%) was statistically “more credible”(p<0.005) than either albuterol inhaler (73%) or placebo inhaler (66%).

For the objective testing, there was a powerful medication effect, but no placebo effect. For the subjective outcome, the placebo effects were equivalent to the active medication effect, and all were better than no intervention. Placebos offered no objective bronchodilator effect beyond no intervention of any kind. Incredibly, subjective improvement for placebo was similar to active drug, even though active drug had 3 times the bronchodilator effect and placebo was no better than no intervention.

In this well designed study, with the inclusion of a “no intervention” arm, the authors are able to demonstrate that placebos are primarily detectable in subjective outcomes, and that studies reporting only subjective results should be interpreted with extreme caution.

Don’t trust the “snake oil” study if it relies on subjective results, rather than objective measurements.



“Liquid Biopsy” for Lung Cancer

The majority of lung cancers are non-small cell carcinomas and about 1 in 5 of those have actionable EGFR mutations that can be treated with tyrosine kinase inhibitors (TKIs), such as erlotinib or gefitinib. Detection of these genetic markers usually involves genotyping of tissue biopsy material. A new “liquid biopsy” may soon change all that. New testing reported recently, using saliva, was able to detect these actionable EGFR mutations with 100% concordance with biopsy-based genotyping. Similarly, plasma genotyping (from blood sampling) for EGFR and KRAS mutations were rapid and accurate. Not only is this testing more rapid (minutes to days versus days to weeks) but it is less significantly expensive, especially if surgical procedures can be avoided. This technology may some day eliminate the need for surgical biopsy. Research and clinical trials are ongoing.

Best way to quit smoking?

Most physicians, including yours truly, have recommended to our smoking patients to quit abruptly (“cold turkey”), rather than slowly cutting down. In a recently published study in the Annal of Internal Medicine, Lindson-Hawley et al examined the success of quitting smoking by gradual means compared to abruptly quitting. This was a study of almost images-3700 smokers in England, and included behavioral support and nicotine replacement. The primary outcome was prolonged validated abstinence from smoking at 4 weeks after quitting and the secondary outcome was validated abstinence at 6 months.

The authors found that, compared to trying to quit by slowly cutting back on your smoking, quitting smoking abruptly was more likely to lead to lasting abstinence, even in those patients who preferred to quit slowly.

Bottom line: You are better off quitting cold turkey.

Teenage vaping increases smoking cigarettes.

E-cigarette usage amongst middle- and high-school students in the US has increased from 1-3% in 2010/2011 to 10-20% in 2013/2014.images-2

In a study from Hawaii, teens who reported vaping were almost three times more likely to try smoking cigarettes over the following year than were their peers who had not used e-cigarettes.

Thomas Wills, from the University of Hawaii Cancer Center, reported in Tobacco Control, regarding a 2013/2014 survey of 2,338 ninth and tenth graders (ages 14-16, avg. 14.7) in Hawaii.

Compared to teens who had never vaped or smoked cigarettes, teens who used e-cigarettes, but not smoked tobacco cigarettes, were 2.87 times more likely to smoke cigarettes within the year.

These data, as well as data from other published studies, indicate that teens who vape are more likely to go on to smoke cigarettes, making a strong case against the sale or use of e-cigarettes to minors as a smoking prevention strategy.

Asthma? Granny’s fault?

In a study presented this year at the European Respiratory Society’s International Congress, research from Sweden suggested that cigarette smoking in previous generations can influence asthma risk in future generations.


There were about 45,000 grandmothers who smoked while they were pregnant with daughters between 1982 and 1986. Of the approximately 66,000 children later born from these daughters, there was a 10-22% increase in asthma risk, even if the mother did not smoke during pregnancy. No cause and effect relationship was established but the findings are of interest and more research is needed.