Tag Archives: asthma

Breastfeeding: protection from asthma

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Good news for breastfed babies –breastfeeding may reduce risk of wheezing and asthma for several years (J Pediatr 2012; 160: 991-6).

In this prospective birth cohort study of 1105 infants from New Zealand, detailed feeding information was obtained at 3, 6, and 15 months which allowed calculation of breastfeeding duration. This information was correlated with information about wheezing and asthma collected at 2, 3, 4, 5, and 6 years.

Findings (after controlling for confounding variables):

  • Each month of exclusive breastfeeding was associated with significant reductions in asthma at all timepoints.  The effect was most prominent at younger ages.
  • The authors estimate that if every infant in the cohort had been exclusively breastfed for 6 months, that asthma would have been reduced by 50% at 2 years, 42% at 3 years, 30% at 4 years, 42% at 5 years, and 32% at 6 years.
  • In atopic children, the effects of exclusive breastfeeding are more pronounced.  In this study, exclusive breastfeeding for ≥3 months reduced asthma at ages 4, 5, and 6 by 62%, 55%, and 59% respectively.

The authors note that not all studies have found that breastfeeding improves asthma.  However, most of these studies reported outcomes in older children.

Related Posts:

Breastfed babies less likely to develop fatty liver

More evidence that breastfeeding improves cognitive development

Additional references:

  • -NEJM 2011; 364: 701, 769.  Living on a farm decreases risk of childhood asthma.
  • -Thorax 2009; 64: 604-9. Breastfeeding and asthma in children followed for 8 years.
  • -Br Med J 2007; 335: 815-20.  Longer time of breastfeeding does not reduce allergy/asthma. n=17,046 pairs of mother-infant (13,889 followed up at age 6.5yrs)

Treating reflux does not help asthma

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Studies in adults have looked at the use of PPIs for asthma and have not shown improvement (see references below).  Now a trial of lansoprazole suggests the same is true in children (JAMA 2012; 307: 373-81).  This study was a randomized double-blind placebo-controlled study of 306 children with a mean age of 11; the participants were recruited from 19 academic medical centers in the US.  149 children received lansoprazole and 157 received placebo.  The dose of lansoprazole was 15mg in patients weighing less than 30kg, and 30mg in those weighing more than 30kg.

Those treated with lansoprazole did no better than placebo with regard to symptoms and lung function.  The main outcome was the asthma control questionnaire (ACQ) score. The lansoprazole group had a mean change in this score of 0.2 units which was not a meaningful change. More precise measures of lung function including forced expiratory volume also did not differ.

In a subgroup of 115 patients who had esophageal pH studies, the prevalence of GER was 43%.  Yet, no treatment effect for lansoprazole was observed for any asthma outcome.

Not only did lansoprazole not help, the treatment group experienced more adverse effects, including respiratory infections (relative risk 1.3), sore throats (RR 1.3), and episodes of bronchitis (RR 2.2).  Though not statistically significant, the treatment group had more activity-related fractures, six compared to one in the placebo group.

This study took several years to complete (2007-2010).  I congratulate the authors, especially the third author Benjamin Gold, for this excellent work.

http://www.ccdhc.org/doctors/gold.html

Additional references:

The Medical Pendulum and Gastroesophageal Reflux

GERD and respiratory/ENT issues:

  • –Gastroenterology 2009; 137: 1844. Critical review of below NEJM article. ‘a subset of asthmatics will have objective detection of GERD without typical symptoms…work by Amer Lung Assn suggests that twice daily PPI will not be helpful’..however, ‘perhaps 3-6months of PPI may still be reasonable until we can accurately identify subgroups of pts who may respond.’ –Gary Falk, Cleveland Clinic
  • –NEJM 2009; 360: 1487, 1551. Use of PPIs (nexium 40mg bid) in poorly-controlled asthma with no symptoms of GER –did not help w asthma control & pH studies were not predictive of response. n=412 adults. 40% c abnl pH studies in each group (nexium vs. placebo).
  • –Clin Gastro & Hep 2007; 5: 1379. Review of ENT findings and reflux.
  • –Am J Gastro 2007; 102: 716. Poor specificity of ENT findings for diagnosis of laryngopharyngeal reflux.
  • –Aliment Pharm Ther 2007; 25: 385-92. meta-analysis. Rx c PPIs not more effective than placebo in resolving ENT symptoms presumed to be due to GER. Editorial suggests some patients may benefit, but better tools are needed to identify them.
  • –Gastroenterology 2010; 139: 1887. PPIs decreased postnasal drainage compared to placebo. n=75. (50% vs 5%) age discrepancy in patient populations.
  • –Clin Gastro & Hep 2010; 8: 741 (excellent editorial), 770 (article on rabeprazole improving heartburn Sx in pts with laryngitis), n=82. Editorial suggests 1-2month trial of BID PPI and if not effective, then little to offer. May change when studies looking at surgery (after impedance) outcomes.
  • –Gastroenterology 2010; 139: 754. 716 (editorial). Acoustic cough & reflux. Study recorded cough during pH measurement. n=71. ‘causality cannot be established until effective treatment’ available.

Common to be “D-ficient”

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Many of the children that a pediatric gastroenterologist sees are at risk for Vitamin D deficiency, including children with inflammatory bowel disease, cystic fibrosis, celiac disease, and liver diseases.  In addition, vitamin D deficiency is widespread: in U.S. 50% of children aged 1-5 years and 70% 6-11 years are vitamin D deficient or insufficient. A thorough review on this “D-lightful” vitamin was in a recent JPEN (JPEN J Parenter Enteral Nutr 2012; 9S-19S).

History: In 1822 Sniadecki recognized children in urban but not rural Poland developed rickets. He postulated the effects of the sun as the reason for rickets; his idea was dismissed.  In 1920s, the concept of irradiating milk to prevent rickets emerged. In 1950s, outbreak of hypercalcemia in infants in Great Britain was thought to be related to vitamin D fortification and curtailed this practice in Europe.  However, these cases were likely due to Williams syndrome.

Sources of vitamin D: oily fish (salmon), cod liver oil, some mushrooms, egg yolk, & sunlight. Exposure of an adult in a bathing suit to one minimal erythemal dose (MED) is equivalent to ingesting 20,000 IUs of Vitamin D. (The minimal dose that induces any visible reddening at that point is defined as one MED.)

Effect of sunscreen: A sun protection factor (SPF) of 30 absorbs approximately 98% of solar ultaviolet radiation & thus lowers vitamin D production by 98%.

Ethnicity: Melanin is an effective SPF.  A person of african-american descent, on average, has an SPF of 15, which reduces vitamin D production by 90%.

Age: Aging decreases 7-dehydrocholesterol in human skin.  Due to this, the elderly produce much less vitamin D.  For example, a 70 year old has a 75% reduction compared to a 20 year old.

Forms of vitamin D:  25-hydroxyvitamin D (25OH-D) is the major circulating form of vitamin D & physicians measure 25OH-D. 25OH-D is metabolized in kidney to 1,25-dihydroxyvitamin D (1,25OH-D), also called calcitriol.  This is the most biologically-active and is responsible for increasing intestinal calcium absorption and mobilizing calcium from bone.  However, 1,25OH-D provides no information vitamin D deficiency; it can be elevated or normal in deficiency states.

  • Cholecalciferol (vitamin D-3) is formed in the skin from 5-dihydrotachysterol.
  • Ergocalciferol (Vitamin D-2) is the form in Drisdol (8000 IU/mL) & Ergocalciferol Capsules (1.25 mg =50,000 USP Units)

Vitamin D deficiency:  The exact numbers are debated.  The institute of medicine (IOM) has considered individuals deficient if 25OH-D is <20 ng/mL.  The Endocrine Society and the author suggest vitamin D deficiency as <20 ng/mL & insufficiency as <30 ng/mL.  The author recommends ideal levels between 40-60 ng/mL.

Consequences of deficiency:

Osteoporosis, Osteopenia, Rickets (see references below): Bone weakening occurs due to loss of phosphorus from the kidneys.  Vitamin D deficiency lowers accrual of calcium in skeleton and leads to osteoporosis, osteopenia, and rickets. Imaging for rickets: the best single radiographic view for infants and children younger than 3 years is an anterior view of the knee that reveals the metaphyseal end and epiphysis of the femur and tibia. This site is best because growth is most rapid in this location, thus the changes are accentuated.

Nonskeletal consequences: vitamin D deficiency is associated with increased risk for preeclampsia, URIs, asthma, diabetes (type 1), multiple sclerosis, hypertension, and schizophrenia.

Treatment:

  • Infants who are breastfed should be receiving supplemental vitamin D, 400 IU/day.
  • Adults/children (>1 year) RDA 600 IU/day –mostly from diet per IOM. Yet author states, “it is unrealistic to believe that diet alone can ….provide this requirement.”
  • In vitamin D deficient patients: (initial treatment) 2000 IU/day or 50,000 IU/week for 6 weeks.
Toxicity from vitamin D (from NEJM 2010; 364: 248-254.): “Toxicity from vitamin D supplementation is rare and consists principally of acute hypercalcemia, which usually results from doses that exceed 10,000 IU per day; associated serum levels of 25-hydroxyvitamin D are well above 150 ng per milliliter (375 nmol per liter). The tolerable upper level of daily vitamin D intake recently set by the Institute of Medicine (IOM) is 4000 IU.”

Additional references:

  • -Pediatrics 2008; 122: 398. Should give 400 IU/day to breastfed babies. Consequences of Vit D deficiency: increased risk for DM, multiple sclerosis, cancer (breast, prostate,colon), rickets, and schizophrenia. Article lists vit D content of foods (high in cod liver oil, shrimp, fortified milk, many fish). Severe deficiency when < 5ng/mL, deficient if < 15 ng/mL; probably should be >32 ng/mL. Causes of vit D deficiency: decreased synthesis (due to lack of sun -skin pigmentation, sunscreen/clothing, geography, clouds), decreased intake, decreased maternal stores & breastfeeding, malabsorption (eg celiac, CF, EHBA, cholestasis), increased degradation; treatment of rickets: double-dose of vitamin d (~1000 IU/day for babies & 5000 for older kids) x 3-4 months along with calcium (30-75/mg/kg/day). Follow Ca/phos/alk phos monthly. Alternatively, give ~100,000 units over 1-5 days.
  • -JPEN J Parenter Enteral Nutr. 2011;35:308-316-Results: The study included 504 IBD patients (403 Crohn’s disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with lower HRQOL (regression coefficient –2.21, 95% confidence interval [CI], –4.10 to –0.33) in CD but not UC (regression coefficient 0.41, 95% CI, –2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). Conclusions: Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.
  • -JPGN 2011;53: 361. similar prevalence of low Vitamin D as general population –58% with less than 32.
  • -JPGN 2011; 53: 11. Guidelines for bone disease with inflammatory bowel disease.
  • -Pediatrics 2010; 125: 633. Increasing Vit D deficiency noted in minority children. n=290. 22% w levels <20, 74% <30.
  • -Hepatology 2011; 53: 1118. Good vitamin D levels are another favorable predictive factor in antiviral response to Hep C along with IL28B.
  • -NEJM 2010; 364: 248-254. Vitamin D insufficiency. Levels between 20-30 may be OK -not enough evidence to determine conclusively whether this level is detrimental
  • -J Pediatr 2010; 156: 948. High rate among african americans with asthma, 86%. n=63.
  • -Pediatrics 2009; 124:e362. n=6275. 9% of pediatric patients vit D deficient & 61% were insufficient.
  • -Pediatrics 2009; 124:e371. n=3577. low 25OH-D levels inversely assoc with SBP/metabolic syndrome.
  • -NEJM 2009; 360: 398. case report of rickets
  • -J Pediatr 2003; 143: 422 & 434
  • -Pediatrics 2003; 111: 908. 200 IU Vit D recommended for all breastfed infants.
  • -J Pediatr 2000;137: 153 & 143.. Nutritional rickets–primarily in blacks; rec vitamin D 400 IU per day.

The Medical Pendulum and Gastroesophageal Reflux

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In so many areas of pediatric gastroenterology, there is a gradual development of enthusiasm for a medical treatment.  In the vast majority, the enthusiasm goes too far and closer scrutiny often determines a more limited role for this medical treatment or potential adverse effects that were not initially appreciated.  The latest example of this may well be with the use of proton pump inhibitors (PPIs) for gastroesophageal reflux disease, particularly in infants and individuals with asthma.  Although these medications may not have reached their apogee, more and more their effectiveness for so many ailments has been questioned.  In this month’s issue of JPGN, this is highlighted (JPGN 2012; 54: 8-14).  The article which emanates from the offices of the FDA discusses the fact that the usage of PPIs has increased 11-fold from 2002-2009 in infants <12months of age; 404,000 prescriptions were dispensed to 145,000 infants in the U.S. in 2009.    At the same time, althougth there have been four randomized controlled trials of PPIs in infants, NO studies have demonstrated the effectiveness of these drugs in this population.  As a consequence, the authors recommend that these drugs be restricted to infants with endoscopically-proven GERD/erosive esophagitis.  No other tools are sufficient to identify infants who are likely to respond.  Perhaps the reason why these agents work less well in infants is due to the fact that acid secretion is much less in infants than in children and adults.  For example, at 4months of life, average acid secretion rate in infants is ~27-fold lower than in adults (Am J Dig Dis 1969; 14: 400-14). As a consequence, their symptoms may not be responsive to acid reduction treatments.

Other related references on GERD in infancy:

–JPGN 2010; 50: 609-18. Pantoprazole helped improve symptoms but there were no significant differences compared to placeblo in withdrawal rates due to lack of efficacy. n=128.
-NASPGHAN 2009, Abstract#21. Meds/Rx of NICU pts did not shorten hospital stay or promote wt gain, n=1149.
–JPGN 2009; 49: 498. NASPGHAN GERD guidelines. “In infants and toddlers, there is no symptom or symptom complex that is diagnositc of GERD or predicts response to therapy.” Identical response to placebo (vs prevacid) in largest double-blind randomized study (54% at 4 weeks) (J Pediatrics 2009; 154: 514-20.)-Reflux is “not a common cause of unexplained crying. irritability..in otherwise healthy infants.” “There is no evidence to support the empiric use of acid suppression for the treatment of irritable infants.”

GERD and respiratory/ENT issues:

–Gastroenterology 2010; 139: 1887. PPIs decreased postnasal drainage compared to placebo. n=75. (50% vs 5%) age discrepancy in patient populations.
–Clin Gastro & Hep 2010; 8: 741 (excellent editorial), 770 (article on rabeprazole improving heartburn Sx in pts with laryngitis), n=82. Editorial suggests 1-2month trial of BID PPI and if not effective, then little to offer. May change when studies looking at surgery (after impedance) outcomes.
–Gastroenterology 2010; 139: 754. 716 (editorial). Acoustic cough & reflux. Study recorded cough during pH measurement. n=71. ‘causality cannot be established until effective treatment’ available.
–Gastroenterology 2009; 137: 1844. Critical review of below NEJM article. ‘a subset of asthmatics will have objective detection of GERD without typical symptoms…work by Amer Lung Assn suggests that twice daily PPI will not be helpful’..however, ‘perhaps 3-6months of PPI may still be reasonable until we can accurately identify subgroups of pts who may respond.’ –Gary Falk, Cleveland Clinic
–NEJM 2009; 360: 1487, 1551. Use of PPIs (nexium 40mg bid) in poorly-controlled asthma with no symptoms of GER –did not help w asthma control & pH studies were not predictive of response. n=412 adults. 40% c abnl pH studies in each group (nexium vs. placebo).
–Clin Gastro & Hep 2007; 5: 1379. Review of ENT findings and reflux.
–Am J Gastro 2007; 102: 716. Poor specificity of ENT findings for diagnosis of laryngopharyngeal reflux.
–Aliment Pharm Ther 2007; 25: 385-92. meta-analysis. Rx c PPIs not more effective than placebo in resolving ENT symptoms presumed to be due to GER. Editorial suggests some patients may benefit, but better tools are needed to identify them.

GERD and surgery:

–Gastroenterology 2011; 141: 1938.  LOTUS study in JAMA summarized in this review. (JAMA 2011; 305: 1969) Medical treatment outperformed surgery. 92% under control (remission) with long term medical Rx vs 85% with surgery & fewer side effects of medical treatment.
–Clin Gastro & Hepatology 2009; 7: 1292, 1264 (editorial). 12yr outcomes for surgery vs PPI. n=154 omeprazole, n=144 surgery. Similar long term outcome ~50% with long term remission.

–Pediatrics 2006; 118:1828. 48,665 antireflux surgeries done from 1996-2003 (~7000/yr) in US

–Clin Gastro & Hep 2006; 4: 299. Frequent complications post-op and frequent need for GERD meds.  Dysphagia in 19%, dilatation in 6%, repeat surgery in 2%, mortality in 0.8% (n=3145). 50% required GERD meds.

–Clin Gastro & Hep 2004; 2: 978-984. Pediatric study.  n=198.  63% required post-op treatment for recurrent GERD -retrospective review 1996-99.

Proton Pump Inhibitors and reported adverse effects:

-Risk of Hypomagnesemmia -2011. http://www.fda.gov/drugs/drugsafety/ucm245011.htm
–NEJM 2010; 363: 2114. large Denmark study. 5082 fetuses with PPI exposure (out of 840,968 live births). Risk of birth defects NOT increased with exposure during 1st trimester. Possible slight increase risk with preconception use except with omeprazole.
–Gastroenterology 2010; 139: 1115. Review of safety of PPIs.
–Gastroenterology 2010; 139: 93. n=167,000. PPIs associated with hip fracture risk, OR 1.3, in patients with other risk factors.
–Gastroenterology 2010; 138: 896-904. 5yrs of PPI -no increase risk in hip/spine fx.
–Arch Intern Med 2010; 170: 765-71, 747 (ed). PP not related to hip fx (n=161,806) women 50-79. INCREASE risk of spine fx, hazard risk 1.47
–Arch Intern Med 2010; 170: 772-8. PPIs increase risk of Clostridium difficile infection (hazard ratio 1.42 –42% increase in risk), n=1166.
–Arch Intern Med 2010; 170: 784-90. n=101,796. OR 1.74 for daily PPI, OR 2.36 if BID Rx; thus ~70% increase risk of nosocomial infection.
–Clin Gastro & Hep 2010; 8: 504. Increased bacterial overgrowth with PPI use.

-JAMA 2009; 301: 2120-2128. Use of PPIs associated with INCREASED hospital acquired pneumonia by ~30%. Could result in 180,000 HAP cases/yr with ~33,000 deaths. n+ 63,878 admissions, 52% on PPIs or H2RAs (83% PPIs, 17% H2RAs). H2RAs NOT associated with HAP cases.
–Gastroenterology 2009; 137: 80. PPIs induce acid-related symptoms in ~22% vs 7% of placebo in healthy volunteers.
–Ann Intern Med 2008; 149: 391-398. Risk for pneumonia associated with short-term PPI use, not long term
–Clin Gastro & Hep 2007; 5: 1418. Increases risk of bacterial gastroenteritis.
–JPGN 2007; 45: 395, 421. Increasing use of PPIs-4-fold from 2000-2003; 0.5% of all infants. No safety/efficacy data.
–J Pediatrics 2007; 150: 262. Long term use (up to 11yrs of usage) of PPIs in 166 children; minimal problems: 2 c nausea, 2 c skin rash, 1 c diarrhea, 1 c agitation.
–JAMA 2006; 296: 2947-53. Risk of bone fracture –odds ratio 1.44-2.65 with long-term PPI treatment (>1yr); UK study looked at 1.8million