Preventing Respiratory Tract Infections

Epistemic Status: pretty confident, typical lit review.  

This report was commissioned by one of my freelancing clients and published by permission.

Bottom Lines

Bacterial immunostimulants are safe and effective in preventing respiratory infections, cutting the risk of infection by 40-50%.

Antiseptic mouthwash and oral care cut the risk of respiratory infection in elderly or ventilator-bound patients by 50-60%, and may also have effects on healthy adults.

Probiotics probably reduce the duration, but not the incidence, of respiratory infections and improve immune function.

Alfa-interferon may reduce the risk or duration of colds, but causes nasal irritation and bleeding that may be more severe than the colds themselves.

Meditation, moderate exercise, and writing personal narratives may reduce the incidence or severity of respiratory tract infections and improve immune function. Spending time in forests and getting massages may improve immune function.

Echinacea and ginseng extracts have mixed and equivocal evidence of effectiveness at preventing respiratory tract infections.

Bacterial Immunostimulants

Bacterial immunostimulants are used in Europe to prevent recurrent respiratory infections. These are made of lysed bacterial cells, and cause both a cellular and humoral immune response, making people more resilient to infections.  A common bacterial immunostimulant, Broncho-Vaxom, can be ordered online, though I can’t vouch for the sites. There are a large number of studies, of which the following are only a selection, confirming that immunostimulants significantly reduce the incidence of recurrent respiratory infections. 

Broncho-Vaxom taken 10 consecutive days per month for three months, tested in a double-blind, placebo-controlled trial of 200 children in a Mexican girls’ orphanage, reduced the incidence of respiratory tract infections by 50%.[1]

In a randomized controlled study of 357 elderly patients with chronic bronchitis, Broncho-Vaxom taken 10 consecutive days per month for three months decreased respiratory infections by 28%.[2]

In a systematic review comprising 851 children, 32% of children treated with Broncho-Vaxom had at least 3 respiratory infections in a six-month period, compared to 58.2% of controls, p<0.001.[3]

In a meta-analysis of 15 randomized trials comprising 2557 patients, polyvalent mechanical bacterial lysate (an extract of multiple bacteria) reduced the incidence of respiratory tract infections by 51%.  These include studies on adults as well as children.[4]

Cochrane’s review, comprising 36 placebo-controlled studies totaling 4060 children, finds that immunostimulants reduce the incidence of respiratory infections by 40% in susceptible children (those who have 3 or more respiratory infections a year.)  Most trials indicated no adverse effects or low rates of adverse effects.[5]

While most of the evidence on bacterial immunostimulants is in children or the elderly, the mechanism of action should be applicable to healthy adults as well, except that it may not have as large an effect if your immune system is stronger.  They are safe and well-tolerated, and the evidence that they prevent respiratory infections in the populations studied is quite robust and consistent.

Oral Hygiene

Using antiseptic mouthwash or even just gargling with water may prevent respiratory infections. There is a lot of evidence for this in the context of patients in the ICU or elderly people in nursing homes, whose oral hygiene is probably worse than the typical healthy adult, but mouthwash makes a large difference there.  There are a few studies on healthy adults suggesting that oral care helps them as well.  Chlorhexidine mouthwash is prescription-only; you can get it from your dentist if you have gingivitis.  

Chlorhexidine gluconate mouthwash reduced respiratory tract infections in patients undergoing heart surgery by 69%.[6]

The rate of nosocomial pneumonia in patients undergoing heart surgery was reduced by 52% in patients given chlorhexidine mouthwash.[7]

A meta-analysis of randomized controlled trials of chlorhexidine gluconate mouthwash in patients on ventilators found that it reduced the risk of pneumonia by 47%.[8]

Oral hygiene (help brushing after meals and regular visits to a dentist) reduced the incidence of pneumonia in nursing homes by 59%.[9]

Gargling with water, in a study on 387 healthy adults, reduced the incidence of upper respiratory tract infections in a 1-month period by 36% compared to controls.[10]

Alpha-Interferon

Alpha-interferon is a protein involved in the innate immune response against viral infection.  Taken as a nasal spray, it can stimulate the immune system against respiratory infections. However, it also has side effects, such as nasal irritation and bleeding.  Interferon is not prescribed as a preventative because of its side effects; however, it is sold online, e.g. here.

In a placebo-controlled study of 448 adults, intranasal alpha-interferon spray given at the onset of a cold in a family member significantly reduced the risk of colds. (1.3% of treated vs. 15.1% of placebo got colds within 2 weeks after spraying, p=0.003).  Overall, this led to a 39% reduction in number of respiratory infections in the treatment group.[27]

In a placebo-controlled study of 229 adults given intranasal alpha-interferon spray over six months, the treatment group got 41% fewer colds.[28]

In a study of 304 adults given intranasal alpha-interferon or placebo, 8.5% of placebo-treated patients got a cold over a 22-day period compared to no interferon-treated. (p = 0.0002).  However, the treatment group didn’t get fewer respiratory infections overall.[29]

Low-dose interferon-alpha spray didn’t significantly reduce the incidence of respiratory infections in a randomized trial of 200 healthy adults.  It did significantly reduce the incidence of moderate-to-severe symptoms in those who had serologically confirmed viral illnesses.[30]

In a randomized trial of 220 subjects with confirmed colds, mucus was 66% less likely to contain cold viruses at day 5-7 in treated patients than controls, and the median duration of colds was significantly longer (9 days) in the placebo group than the treated group (6 days).  Treated patients were significantly more likely to have blood in their mucus than placebo.[31]

Probiotics

Probiotics, especially Lactobacillus and Bifidobacterium species (the kind found in yogurt) have been found to reduce the duration of respiratory tract infections, though not their incidence. Probiotics sometimes enhance immune parameters such as lymphocyte count and NK activity.

In a meta-study of 14 randomized controlled studies comprising 3451 participants, the pooled risk of having an upper respiratory tract infection when given a probiotic was 47% lower compared to placebo.[56]

In a meta-study of 14 RCTs, ten out of the fourteen found no significant difference in incidence of respiratory tract infections between probiotic and placebo, but five out of six found significant reductions in symptom severity.[57]

In a systematic review of 20 RCTs, probiotics significantly decreased the duration of respiratory tract infections (by about a day) and resulted in significantly fewer days absent from school/work due to respiratory tract infections.[58]

In a Cochrane review of 12 RCTs, probiotics significantly reduced the duration and incidence of upper respiratory tract infections, in both children and adults; however, the quality of evidence was low.[59]

In a study of 1072 elderly volunteers randomized to a fermented dairy product containing Lactobacillus casei or a control dairy product, treated patients had significantly shorter duration (by 4 days) of upper respiratory tract infection. [60]

In a study of 47 military recruits randomized either to a fermented dairy product containing Lactobacillus casei or a placebo dairy product, there was no difference in the incidence of respiratory infections.[61]

In 30 healthy elderly subjects, Bifidobacterium lactis but not control significantly increased the number of lymphocytes and NK activity.[62]

In a controlled study of 50 healthy Taiwanese subjects aged 40-81, Bifidobacterium lactis HN019 significantly increased NK and CD4+ activity over a period of 6 weeks, while milk alone did not.[63]

In one study on 20 healthy subjects aged 40-65, Lactobacillus casei strain Shirota had no effect on immune parameters.[64]

However, in a study of 30 elderly subjects, Lactobacillus casei strain Shirota caused significantly higher NK activity compared to placebo. [65]

And in a study of 20 subjects, both elderly and young, Lactobacillus casei strain Shirota caused significantly higher NK activity compared to baseline or placebo.[66]

Fermented dairy products containing probiotics are safe and probably somewhat helpful for promoting recovery from respiratory infections.

Psychological Interventions

It’s well known that psychological stress can weaken the immune system; stressful events like bereavement or studying for exams, as well as depression and anxiety disorders, increase susceptibility to infection. Some psychological interventions also reduce the risk of respiratory infections or have more indirect immune-stimulating effects.  These include meditation, written emotional expression (writing about traumatic and emotional experiences in your own life), massage, and forest bathing (spending several hours walking mindfully in a forest.)

Meditation

An 8-week mindfulness meditation course significantly increased (p < 0.05) antibody titers in response to a flu vaccine.[38]

An 8-week meditation course reduced days of work lost to respiratory infections by 76% (p < 0.001) and global severity was significantly lower for meditation than control (p =0.004).[39]

A guided relaxation exercise with imagery increased NK activity (p < 0.05) in an uncontrolled study on 10 healthy subjects.[40]

In a randomized trial of 48 patients with HIV, those enrolled an 8-week mindfulness meditation course had significantly (p = 0.02) higher CD4+ T lymphocyte counts than patients in the placebo 1-day course.[41]

In a trial of 28 patients with breast cancer randomized to either a 10-week mindfulness-based stress reduction class or no intervention, the treatment group had significantly more lymphocyte proliferation than the controls.[42]

Written Emotional Expression

Written emotional expression — being prompted to write about “the most traumatic and emotional experiences of their lives” — for thirty minutes at a time for four consecutive days — in HIV patients raised their CD4 count gradually over a period of 6 months and instantly dropped their viral load, p=0.024 and p=0.035 respectively.[43]

40 medical students randomly assigned to write about traumatic personal experiences or control topics for 4 consecutive daily sessions had significantly higher antibody titers in response to a hepatitis C vaccine.[44]

In a study of 50 healthy undergraduates randomized to either writing about personal trauma or control topics for 4 consecutive daily sessions, those who wrote about trauma were significantly less likely to visit the health center for illness, and had stronger lymphocyte increases in response to mitogens.[45]

Forest Bathing

Shinrinyoku, or “forest bathing” — a three-day trip to a forest, spending a total of 3 hours walking outside — increased NK counts significantly (p < 0.01) while a three-day city tourist visit did not.[46]

Out of 12 male subjects taken on a 3-day “forest bathing” trip, 11 had significantly increased NK activity (by about 50%)[47]

Massage

Back massages, but not progressive muscle relaxation therapy, significantly increased (p<0.05) CD4 count in adolescent girls with HIV.[48]

Full-body massage in women undergoing radiation therapy for breast cancer significantly attenuated the drop in NK activity compared to controls.[49]

Compared to light touch, Swedish massage significantly increased the number of lymphocytes in 53 healthy adults.[50]

Compared to no massage, a month of daily massage significantly increased NK count, NK activity, and CD8 lymphocyte count in 29 gay men.[51]

Exercise

Moderate exercise can prevent respiratory tract infections and improve other measures of immune function.  However, very intense exercise (as in marathon training) increases susceptibility to infection.

Cardiovascular exercise, but not flexibility exercise, prolonged seroprotection from the flu vaccine (increasing the percentage of subjects who were still protected at 24 weeks by 30-100%.)  People in the flexibility group reported no more respiratory tract infections, but reported them as being less severe (p = 0.03).[52]

An 8-week exercise course reduced sick days from respiratory infections by 52% (p = 0.042).[39]

A program of treadmill exercise in elderly women significantly (p < 0.05) increased NK activity relative to sedentary controls.[53]

An exercise program (brisk walking 5 times a week) significantly (p < 0.001) increased NK activity and cut the duration of respiratory infections in half compared to control in a study of 36 sedentary women.[54]

Endurance athletes, compared to the rest of the population, experience more upper respiratory tract infections around training and competition. In non-athletes, higher rates of physical activity are associated with lower risk of upper respiratory tract infections.[55]

Echinacea

Extract from Echinacea purpurea or Echinacea angustifolia (purple coneflower) reduces the incidence of respiratory infections in some but not all studies.  The largest and most stringent meta-analyses have concluded that echinacea extracts don’t prevent respiratory infections, but it’s possible that some preparations are effective, more likely alcoholic extracts than pressed juice.

A meta-analysis comprising 1630 patients found that echinacea reduced the probability of a patient contracting a cold by 58%, p <0.001, and reduced the duration of colds by 1.4 days, p < 0.01.[11]

A subsequent meta-analysis of 6 clinical studies comprising 2458 participants found that echinacea caused a 35.1% lower risk of recurrent respiratory tract infection than placebo.  Alcoholic extracts reduced the risk of recurrent infections by 45%, while pressed juices did not have a significant effect.[21]

A meta-analysis of 14 studies  where subjects were experimentally infected with rhinovirus, comprising a total of 2040 patients, found that the likelihood of experiencing a clinical cold was 55% lower in patients treated with echinacea than controls, and the duration of a cold was 1.4 days lower with echinacea vs. placebo.[12]

In a structured meta-analysis of 9 studies of echinacea on the common cold, the only two studies that met all criteria for high-quality experimental design was negative, while the other studies, which tended to have positive results, usually lacked proof of blinding.[24]

In a Cochrane review of 24 double-blind trials comprising 4631 subjects found that echinacea extracts had no significant effect on preventing colds, though there were non-significant trends towards an effect.[26]

A study of 430 young children randomized to echinacea, propolis and vitamin C extract or placebo for 12 weeks found a 50% reduction in the number of respiratory tract infections per child in the treatment group.[13]

A randomized controlled study of 302 adults at military institutions or an industrial plant found no difference between echinacea ethanolic extract and placebo in the incidence of respiratory tract infections over a 12 week period.[14]

In a randomized controlled study of 432 volunteers experimentally given rhinovirus, echinacea alcohol tincture had no effect on the incidence or severity of colds.[15]

A randomized controlled trial of 128 adults given echinacea pressed juice or placebo at the onset of a cold found no significant difference in symptom severity or duration.[16]

In a randomized controlled trial of 282 adults given echinacea tincture or placebo, symptom scores were 23% lower for echinacea than placebo.[17]

In a randomized study of 524 children randomized to echinacea juice or placebo after getting a single respiratory infection, the treatment group was 24% less likely to get another respiratory infection over a 4-month observation period.[18]

In a randomized controlled trial of 90 hospital staff members, those treated with echinacea did not significantly alter the risk of upper respiratory tract infections.[19]

In a randomized study of 48 adults infected with the common cold and given echinacea pressed juice or placebo, echinacea did not significantly reduce incidence of colds.[22]

In a randomized study of 719 adults with new-onset common colds, echinacea extract didn’t significantly reduce severity or duration.[23]

In a randomized study of 755 subjects given either an alcohol extract of echinacea or placebo, the echinacea-treated patients had 21% fewer respiratory infections over a period of 4 months.[25]

Echinacea extract is safe, and may have some effect on preventing respiratory infections, but the evidence is inconsistent and equivocal.

Ginseng

There are some studies providing positive evidence that ginseng reduces the incidense of respiratory infections, but the meta-studies show that overall its effects are non-significant.

A systematic review comprising 747 patients found that there was “insufficient evidence to conclude that ginseng reduces the incidence or severity of common colds” — there was a trend towards reduced incidence of colds, but this wasn’t statistically significant.[32]

In a randomized study of 323 adults with a history of at least two colds in the past season given American ginseng (Panax quinquefolium) extract or placebo reduced the average number of colds per person in a four-month period by 27%, from 0.93 in the placebo group to 0.68 in the treated group.[33]

In a randomized study of institutionalized elderly subjects treated with American ginseng extract or placebo, treated patients had 85% less chance of getting influenza (p < 0.033) and 89% less chance of getting any acute respiratory infection (p = 0.009).[34]

In a study of 323 healthy volunteers randomized to COLD-FX (a ginseng extract) or placebo, there was no effect from the treatment on the number or duration of colds.[35]

In a study of 783 adults treated with American ginseng extract or placebo, ginseng did not significantly affect the number of laboratory-confirmed respiratory infections.[36]

Panax ginseng extract significantly (p < 0.001) increased NK cytotoxicity (a measure of immune function) over placebo.[37]

Ginseng extract is safe and may have some immunostimulant activity, but there’s only weak evidence that it prevents respiratory infections.

 

References

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23 thoughts on “Preventing Respiratory Tract Infections

  1. I must confess to not understanding all of this so I have a few quick questions. Just to clarify, when you mention that a study showed a reduction in respiratory infection or upper respiratory infection, does that cover both bacterial infection and viral infections, or is the research limited to one or the other?

    A lot of the interventions were stuff I’d naively expect to be useful in managing bacteria, (mouthwash, probiotics etc.) but wouldn’t expect to do much about viral infections like the common cold. But it kind of reads like it does. If it does cover stuff like the common cold, that’s very cool. Broadly speaking, is the take away that if I as relatively healthy adult in a western developed country start taking Bacterial immunostimulants and using antiseptic mouthwash before I go to sleep, I can significantly reduce the frequency that I get colds?

    Also, do you have a sense of the value add of the anti-gingivitis mouth wash vs. something Listerine? I.e. how much effort should a reasonable person make to obtain prescription mouthwash?

    Lastly and most importantly, thanks for putting this together and posting this. These research collection posts are probably a ton a work to put together, and I really appreciate them and think they are great. Just wanted to say thanks for the work that you share here.

    • “Upper respiratory tract infections” are the standard term in the literature and they include both bacterial and viral infections. The info on mouthwashes mostly focuses on pneumonia, since that’s a major cause of death in the elderly and people on ventilators; in the latter population, most pneumonia comes from antibiotic-resistant bacteria. The probiotics literature has a lot of examples of viral infections and colds.

      I am not sure about the value-add of prescription mouthwash since there just aren’t that many studies of this in healthy non-nursing-home-living people, except for the one study which found that water gargling made a difference (so presumably non-prescription mouthwash should too.) FWIW, if you bleed every time you brush your teeth, you probably have enough gum disease to warrant getting a prescription.

  2. What about wearing masks? https://www.healthline.com/health/cold-flu/mask A habit worth importing?

    I’ve been thinking about animal husbandry and low cost disease monitoring, along the lines of tiny mass produced wearable or implantable devices that can detect unusual patterns…. Like a cow fitbit… And more quickly isolate infected individuals from the herd. Having a mic that can detect sneezes and coughs by the animal wearing it sounds simple enough. But to apply that to humans, I wonder whether it would work to pay people to implant disease monitoring devices, which would alert authorities to isolate them if they fell ill. As part of the deal, pay the victim and the victim’s employer enough that they are glad to fall ill/have an employee go briefly AWOL. Abuse could be prevented by the cheap multifactor authentication of movement, temperature, and respiratory factors.

    You scan red, sir! It’s your lucky day!

    I do find it irritating that we’ve already totally signed away our privacy, but people won’t cash in on the opportunities opened up by having that cost sunk.

  3. “Safe” seems like a bit of an exaggeration for bacterial lysates for prevention given the lack of any apparent long-run trials. The Algernon principle suggests that boosting the immune system through positive interventions is costly. It could be that this is just a calibration thing, and people without autoimmune problems but with frequent infections should try this, but it could easily instead be the case that it fucks you up in some way that’s subtle initially but devastating long-term.

    On the other hand, our immune systems are plausibly just chronically understimulated by the modern environment. In that context, this could fit in with probiotics, meditation, sleep, as rectifying harmful things about the modern environment.

    More along the lines of “don’t do marathons” would be especially helpful; cessation of harmful practices seems especially likely to be safe.

    • The Algernon principle occurred to me as well, but one possible answer is the energy cost of running the immune system — this would have mattered historically, but not so much in our modern calorie-rich world.

  4. A “lit review” typically consists of more than a dull laundry list of references. FYI: research is more than just plugging in obvious search terms into Google Scholar and compiling one-sentence summaries of the abstracts. This is almost totally valueless and I don’t know why anyone would pay money for this crap. It shows no evidence of substantive engagement at all, which is the only reason why someone would read a lit review rather than just using scholar.google.com themselves.

    • And yet, I’m pretty sure most people don’t know this stuff until Sarah does a post like this. Seems like this is an opportunity for you to either (a) provide a substantial public good at very low cost to yourself or (b) learn that what Sarah’s doing is harder than it looks.

    • FWIW, a proper systematic review, of the kind Cochrane publishes, takes about a year, and costs an estimated $1M of researcher time. In 10-20 hours of work, I obviously don’t do anything that thorough. But I don’t believe that in general one can only get value from either the “gold-plated edition” or nothing.

      I am very transparent with my clients about what they get from me — there are lots of examples that I make publicly available, such as this one — and as long as they’re happy, I’m not going to quit what I’m doing just because someone on the internet calls it “crap.”

  5. Have you also read the theory of how respiratory tract infections work, how the immune system works, etc.? If not and if you only looked for studies and meta analyses, it is plausible that you have missed something important. asdf’s comment makes me cautious.

    • Obvious mistakes or omissions I’ve noticed in 5 mins of skimming:
      – interferon alpha is NOT the same thing as interferon alfa, and the post does NOT clearly distinguish between the two, or even seem to recognize the difference, despite recommending interferon alfa
      – there is NEARLY ZERO discussion of plausible mechanism of action WHATSOEVER — and ANYONE with any training in medicinal chemist, or common sense, will realize that mechanistic considerations give you a very informative prior about whether or not you should believe borderline results at all, or whether undesirable side effects may manifest
      – it does not discuss anywhere what a respiratory tract infection is, why we should care, how common/severe they are, …
      – were the studies controlled properly? are there any possible caveats? what are plausible confounders? what about reviews other people have written? is this literally the first lit review of respiratory tract infections ever? ???
      – there is NO DISCUSSION of the side effects of broncho-vaxom — which exist (as you can verify for yourself).

      like, just open up Nature Rev Drug Discov, and open up ANY article, and just look at how different it is from this total mess of a “lit review”. it is NOT “typical”. do NOT fall for this scam.
      I’ll even point out that it’s so dense, tedious, unmotivated, and laundry-list-like that almost nobody is going to read it, let alone read it fully, so any benefit this “lit review” may provide to the public is substantially attenuated by that alone

      • let me reiterate that it’s not clear to me if Mrs. Constantin actually understands the meanings of all the words she used in this post, which is honestly not a high bar

      • interferon alpha is NOT the same thing as interferon alfa, and the post does NOT clearly distinguish between the two, or even seem to recognize the difference, despite recommending interferon alfa

        Seems worth correcting Wikipedia, then, which seems to think that interferon alfa is literally just made of interferon alpha. What’s the difference?

        I agree that some discussion of mechanism would have been very helpful in contextualizing this stuff. Likewise with assessments of study quality – it’s somewhat difficult to assess evidence strength without a model.

  6. I’m happy I found this site and thank you for sharing this. Quick question: any particular reason Vitamin D is missing? I’d have expected it somewhere near the top.

  7. I think you may be resisting banning the user named asdf, despite their extremely rude behavior, either because you don’t like banning people in general, or because you (as I) are reluctant to ban someone who disagrees with you, even if they do so extremely rudely, because you are concerned it looks like you can’t answer their criticism.

    I would like to counter this instinct, by pointing out that keeping rude commenters around makes other people less likely to engage with the comment section of your posts. This is true even if the rude commenter sometimes says accurate things. Reading rude comments is aversive.

    I strongly encourage you to enforce civility in your comment section, even if you are reluctant to do so.

    See also http://lesswrong.com/lw/c1/wellkept_gardens_die_by_pacifism/ .

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