Smoking is bad for you, so why another study?

This is a coffee-break-read, i.e., a brief comment on a recent paper found in a casual google scholar search on ADPKD.

The paper:

Brody JS, Wang W, Schrier RW, Gitomer BR (2015) Effects of Smoking on ADPKD: Frequency of Vascular Events and Concentrations of Soluble CD40 Ligand. General Med 3:175. doi: 10.4172/2327-5146.1000175

A study from the University of Colorado, renal department, main author is a biologist with lots of papers on cardiovascular risk factors to her name.

Hypothesis: 

“Current cigarette smoking enhances pro-inflammatory responses in ADPKD patients and thereby enhances cardiovascular and renal damage.” 

I struggled a bit on whether this was anything worth reading, after all we all know that smoking is bad for you and why would patients with ADPKD be any different. The premise they use to justify the paper is that cardiovascular events are THE leading cause of death in ADPKD patients now that renal replacement therapies are used  – that is, we don’t die from renal failure so much as heart attacks and strokes.

The study population (patients): 

There are 3 patient groups mentioned in this paper and they try to bring the results together but in reality they form completely different cohorts and have different and points.

Group 1 was from a longitudinal observational study dating from 1985 to 2001 and they used from this group around 350 smokers and a similar number of non-smokers.  I am assuming they mean “never-smoked” but the paper is not actually clear on this point. This group were analysed for any cardiovascular or cerebrovascular event to see if the smokers had more than the non-smokers (no spoilers, don’t go guessing the results yet).

Group 2 were from a self-reported survey of ADPKD patients in 2011/12 of which 159 were smokers and 259 non-smokers.  The authors do not state the primary purpose of the survey or how participants were selected.  They asked about CVS events under three questions – effectively head, heart and legs.  There are no laboratory values for this group or external validation of the responses it seems.

Group 3 was the smallest but perhaps the most interesting sub group where they took 40 patients, 20 each smoking/non-smoking, and measured the serum CD40 ligand (sCD40L).  This protein activates cell-mediated immune functions that in turn lead to an increase pro-inflammatory cytokines – in simple terms the molecule is a marker for increased inflammation going on in the body, though it is non-specific for renal disease or cardiovascular disease.  It appears to be a fashionable molecule to measure as there are many papers looking at it in different populations.

The results: 

You have probably guessed: SMOKERS HAD MORE CARDIOVASCULAR EVENTS.

Group 1 smokers were also noted to have higher amounts of protein in the urine.  Now this is an odd one because protein in urine isn’t particularly found in ADPKD though if it does occur it might indicate that the disease is approaching and end-stage renal impairment.  The authors make an even odder statement that smoking is associated with proteinuria in middle-aged Japanese men – that may be so but the study isn’t in Japan, included women and so I was left pondering the relevance of this random sentence.

Group 2 patients of course also showed higher numbers of CVS events in smokers, did you expect anything else?

The sCD40L was found to be higher in smoking ADPKD patients than never-smoked ADPKD patients.

Having got thus far I was still left wondering what this study adds to current common knowledge.  It seems more likely that a junior in the department needed a publication to their name and so scrambled together some data in an attempt to support a cobbled hypothesis.

Comment: 

The authors acknowledge the limitations of this paper — small numbers of events, insufficient detail in smoking data (they did not ask about or calculate pack-years) and based half of their conclusions on patient-reported surveys.

The bottom line is still: SMOKING IS BAD FOR YOU, whether you have ADPKD or not.

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