Ian J. Kahrilas|Peter J. Kahrilas
Reflux Disease and Idiopathic Lung Fibrosis
Loyola University Chicago|Northwestern University
related article see page 33in issue chest mthot et al1mthot db leblanc lacasse metaanalysis gastroesophageal reflux disease idiopathic pulmonary fibrosischest 2019 155 3343abstract full text full text pdf pubmed scopus 47 google scholar conduct methodologically elegant metaanalysis 18 casecontrol studies exploring relationship gastroesophageal reflux disease gerd idiopathic pulmonary fibrosis ipf concluding ipf gerd indeed weakly associated 294 95 ci 195442 however importantly suggest association clinically meaningless essentially evidence causal relationship rather apparent association ipf gerd attributable confounding bias cigarette smoking likely cause ipf substantially prevalent amongst case subjects control subjects constituent trials metaanalysis indeed despite emerging hypothesis ipf stems genetic mutations epithelial lung cells likely consequence smoking one 18 studies included matched proportion smokers exsmokers groups one accounted smoking multivariate regression models post hoc metaregression controlled smoking mthot et al1mthot db leblanc lacasse metaanalysis gastroesophageal reflux disease idiopathic pulmonary fibrosischest 2019 155 3343abstract full text full text pdf pubmed scopus 47 google scholar found gerd ipf unrelated nine studies 066 95 ci 034127 also found substantial heterogeneity diagnostic methods emphasizing gerd neither easily consistently defined highlights two important issues 1 distinction association causation 2 inconsistencies definition gerd among clinical study populations related article see page 33 historically observational epidemiology invaluable identifying environmental risk factors disease cholera contaminated well water scrotal cancer working chimney sweep classic situations leap association causation small strength association overwhelming mortality chimney sweeps scrotal cancer 200 times unexposed colleagues2hill ab environment disease association causationproc r soc med 1965 58 295300pubmed google scholar however reported associations weak case gerd ipf 4 casecontrol studies3grimes da schulz kf bias causal associations observational researchlancet 2002 359 248252abstract full text full text pdf pubmed scopus 924 google scholar confront limits observational epidemiology making leap association causation treacherous without benefit randomization selection bias informational bias andor confounding bias result spurious associations favorite textbook example association ice cream consumption gun shootings brought commonality association warm weather akin current study linking oral contraceptive use myocardial infarction failing recognize cigarette smoking real culprit strangely prevalent amongst oral contraceptive users3grimes da schulz kf bias causal associations observational researchlancet 2002 359 248252abstract full text full text pdf pubmed scopus 924 google scholar yes treating ipf proton pump inhibitors ppis like limiting ice cream consumption hopes curtailing gun violence stopping birth control pills prevent heart attacks current american thoracic societyeuropean respiratory societyjapanese respiratory societylatin american thoracic association guidelines recommend antiacid treatment patients ipf4raghu g idiopathic pulmonary fibrosis lessons clinical trials past 25 yearseur respir j 2017 50 pii 1701209crossref scopus 78 google scholar absence highlevel evidence benefit expert opinion accepted hypothetical disease model causation conflicting observational studies treatment benefit render conditional recommendation antiacid treatment however subsequent scrutiny observational trials reporting benefit ipf survival ppi treatment found uniformly flawed immortal time bias nonppi users risk death immediately enrollment ppi users defined 12 months ppi exposure making immortal period guaranteeing would survive minimum 12 months5tran suissa effect antiacid therapy survival idiopathic pulmonary fibrosis methodological review observational studieseur respir j 2018 51 pii 1800376crossref pubmed scopus 34 google scholar recognizing error european treatment guidelines revised advise gerd treatment ipf degree mandated gerd symptoms6behr j gnther bonella f et algerman guideline idiopathic pulmonary fibrosis update pharmacological therapies 2017pneumologie 2017 71 460474pubmed google scholar leads issue study heterogeneity raised mthot et al1mthot db leblanc lacasse metaanalysis gastroesophageal reflux disease idiopathic pulmonary fibrosischest 2019 155 3343abstract full text full text pdf pubmed scopus 47 google scholar gerd defined defined gastroesophageal reflux normal asymptomatic event meals becomes disease gerd reflux stomach contents causes troublesome symptoms andor complications7vakil n van zanten sv kahrilas p et althe montreal definition classification gastroesophageal reflux disease gerd global evidencebased consensusam j gastroenterol 2006 101 19001920crossref pubmed scopus 2709 google scholar umbrella definition widely referred montreal definition devised encompass endoscopically evident disease reflux esophagitis stricture barretts metaplasia troublesome esophageal symptoms without endoscopically evident disease heartburn regurgitation chest pain potential extraesophageal manifestations laryngitis cough definition goes define troublesome sufficient frequency andor intensity impart measurable decrement quality life hence neither abnormal phmetry absence symptoms attributable reflux nonspecific symptoms absence established reflux causation meet definition however among 18 studies included mthot et al1mthot db leblanc lacasse metaanalysis gastroesophageal reflux disease idiopathic pulmonary fibrosischest 2019 155 3343abstract full text full text pdf pubmed scopus 47 google scholar metaanalysis gerd diagnosis based solely phmetry 11 solely symptom inventory five inferred diagnostic code entries two bottom line idea proportion subjects actually met current definition gerd summary interpretation weak associations observational data limited hypothesis generation qualified accordingly statistically significant associations beg point whether association clinically meaningful may statistically precise precisely incorrect8grimes da schulz kf false alarms pseudoepidemics limitations observational epidemiologyobstet gynecol 2012 120 920927crossref pubmed scopus 192 google scholar statistical associations emerge next step scrutinize study bias judge type association exists spurious indirect causal2hill ab environment disease association causationproc r soc med 1965 58 295300pubmed google scholar 3grimes da schulz kf bias causal associations observational researchlancet 2002 359 248252abstract full text full text pdf pubmed scopus 924 google scholar mthot et al1mthot db leblanc lacasse metaanalysis gastroesophageal reflux disease idiopathic pulmonary fibrosischest 2019 155 3343abstract full text full text pdf pubmed scopus 47 google scholar demonstrated misunderstanding relationship gerd ipf spurious indirect propagated misunderstanding overtreatment ppis magnify analogy numerous syndromes associated gerd wonder estimated 8 9 us adult population using ppis9kantor ed rehm cd haas js et altrends prescription drug use among adults united states 19922012jama 2015 314 18181830crossref pubmed scopus 781 google scholar thoughtful utilization ppis revolutionized treatment acidrelated disorders indiscriminate use exposed population unopposed risk10yadlapati r kahrilas pj dangers chronic proton pump inhibitor usej allergy clin immunol 2018 141 7981abstract full text full text pdf pubmed scopus 27 google scholar indeed lack statistical literacy proliferationacceptance flawed studies risk benefit overwhelmed proper critical analysis ppi treatment role sponsors sponsor role design study collection analysis data preparation manuscript metaanalysis gastroesophageal reflux disease idiopathic pulmonary fibrosischestvol 155issue 1previewthe relationship gastroesophageal reflux disease gerd idiopathic pulmonary fibrosis ipf controversial current guidelines recommend clinicians use regular antacid treatment two recent metaanalyses antacid therapy ipf inconclusive objective study examine evidence regarding association gerd ipf systematic review metaanalysis special reference methodologic quality observational studies fulltext pdf