& nutrients Review Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment eva Scot, Marika Massaro, Sergio Garbarino 0 and Domenico Maurizio Toaldo? "Nato Resch Coun (CNR) te of Cl Phy ogy ORC), 7300 Ls ay, ‘mara naeunescenrt 2 Depart of Neuen Resbititn, Ophulnology Genes and Maternal Snes, Universo Gon 16132 Geno Rly putrinneroga com 3 Ruban pate Cao Raspioy Cae Uni V Fa Hop AS La, 7300 Las, aly orale + Comespondenc: por scoteccnis Ta: 9-0-8860 Receive: 29 April 2019; Aecepted: 14 June 209; Published: 16 June 2019 Seats Abstract Chronic structive pulmonary disease is ane ofthe lading uses of morbidity and rmortaliy worldwide anda growing healthae problem. Identifation of modifable isk factors for prevention and tcatment of COPD urgent, and the scenic community has begun pay ‘lowe attention to dita an integral part of COPD management frm prevention to tetment Tht review summarins the evidence from observational and linc sties regarding the impact of rutin and etary pattems on lung funtion and COPD developmen, progression, and outcomes, ‘with highlights on potential mechanisms of action. Several dietary options can be considered in terms of COPD prevention andjce progression. Although deft data are lacking, the avaiable ‘inti eidence nates that sme foods and utes, especially thos traces endowed ‘ith antioxidant and an-inflammatory propertis and when consumed in combinations i the Form of lance dietary pattems, are associated with Better pumonary function, les hing netion decline, and reduced sk of COPD. Knowledge of dletary inuences an COPD may provide heals _rofesionls with an evidence-based itty appreuh tobi cour! paint treed improved ‘lmonary esth Keywords antondant chronic obstractve pulmonary dies dietary pate inflammation ing, funtion; Mesiterranean diet rutition oxidative ses; pelyphenel polyusaturated faty ac 1. Introduction ‘Chron obstructive pulmonary disease (COPD) i mujor cause of moeidity and mortality and helthare burden weridwide, acting around 10% of he ad populations aged 40 years and ‘older, According to WHO estimates manly from high-income counties, 65 milion people have moderate to severe COPD, but a great proportion of COPD workwide may be underdiagnosed, ‘mol i low and middle income countries, COPD burden is projected to dramatically increase dec to cao exponure to ia facie ane the changing age aructure ofthe word population and isexpecte to be the third lending couse of death werwide by 2030 (WHO 2019, Barden of COPD hepwrvhanspiatryeopalbundenen). Therefor, prevention and management of COPD Iscureny considered a mor health problem, with important socal and economic sues, ‘COPD encompasses «group of dsrders, including smal airway obstruction emphysema, and ‘hrc bronchitis, and is characterized by elon inlsmeation of te aeways and lang parenchyma ‘vith progresive and areverubl iow lito [2]. Symptoms of COPD include dyspnea (distess ‘with breathing), cough, and sputum production. The natural history of COPD is punctuated by it 20,01 05, aaa BE ncnrecurrent episodes of acute exacerbations which often require hospitalization and negatively affect, atents’ quality of fe, aclerate teat of deine in ang function and are associated with morally Diagnosis nsesment and management of COPD are mostly guided by the degree of sion lution as moe bythe forced exper volume in one second (FEV), forced vial eapacty FV), and FEVI/FVC rai, although other phyilogical measurements ich asthe nsprstory capacity total ang capacity (TLC) rao, arteral blood gases, and exercise capacity prove complementary Information on the sever of the disease [To acount forthe complet of the disease and adn, In disease severity assesment, multidimensional indices mainly based on cline and functional pramers have been developed, However significant heterogeneity sn tem of cin presentation, Dhyniclogy, imaging, neponse 16 therapy, hing fancion decline, and survival exist in COPD, ‘hllenging the overimplifation regarding definition and assessment of COPD and leading tert In ideniying subgroups of patients aed phenotypes, resulting fom diferent endotypes(bilogi rechanistns) and displaying distinct prognostic and therapeutic vale, Accondingly, several COPD. ‘Phenotypes have boen recently describes, which exhib significant dierences in age, symptoms, ‘comorbidities, and priced mortality [-7]. Most studies described COPD heterogenity using ‘mite range of warble, nin some esses the cin relevance of identified phenotypes eds ‘be determined (8), Despite these current limitations, the phenotypic characterization of COPD paints ‘wth insight into the underlying biological proces and relied bomarkars may ultimately allow or [tierra srlifcation and personalzan of therapies “The predominant rk factor for COPD developments former or current tobacco smoking However not all smokers develop COPD, suggesting that other envionmental factors are also Involved, including outdoor and indoor ar pollution (eg. blomass fuel exposure), occupational Ihazards infections, and second-hand smoke during pregnancy or etl childhood. Furthermore, genetic susceptbilty (eg, deficiency im at-antrypsi) and epigenetic nuances have also been implicates in the pathogenesis of COPD [0 Recent new insights suggest that these diferent factors _may impinge on lung function and recprcally interct starting ery in ie Le, in utero and during ‘aly childhood), this determining many potent trajectories ofthe natal course ofthe disease, ‘which list predipon tothe development of COPD and its differen nicl appearances a well {sof cher coetng chronic dneoes inner ie [1011 With ear to COPD management, he most important pblic health message remain smoking «station, but the mutfctoral ature of COPD requires attention to other modifiable isk fatrs ‘Compared with other chon dieses wit sar burdens on qual of ie and bealhare costs, such 1s cancer and cardiovascular disease (CVD) les known abut how Mest factors other har and Independant of—amnoking influence pulmonary function and the development of COPD. Dit has ‘been noyaized a a mndfiable ak factor for chronic diseases developenert nd progression [12, and recent evidence has also incessingly pointed to a rele in obstructive lung diseases, including {COPD 5-15} important changes in det over the pst ew decades, with deceased consumption of frais, vegetables, wholegrains and sh, and increased consumption of proceed and refined foods, dave ben invocted fo entrhue to the inrened prevalence of don disene, nctoding COPD, ‘mainly in developing count. Distary factors may modulate the impact of adverse environmental exposures or genetic preepoiton am the hing [6] bt can also have direct (protective or harm efets on the bogs processes involved in hing function, disease development nd outcomes [7,8} The impact exerted by earlyie and cumulative dietary choices on atric health has been increasingly recognized ‘Se vespainydioonc ths oflring a greater window of oppectnity foe ane prevention [9] urthermore, the abnormal nition ste observed in advanced COPD patients, th intend ‘weight os, muscle Tos, low fat and at-ree mass associated with the presence of emphysema Isa recognized independent determinant of COPD outcomes and provides targets fr uttonal Interventions [20]. On the other hand although the phenomenon ofthe obesity parades, Le, he rognestc advantage of increased body mass index (BMI in COPD (ue othe reduction n satevolume), hasbeen report the alo abdominal viscera aposty compared with subeataneous fat In exacerbating the pro-inflammatory state and the CV risk inpatients with COPD deserves clinical tention and treatment [2], mostly because aft redstbuton foward more visceral fat and an ‘ocited increeed apace sats have ben shown in ld-tornderabe romohee atone with COPD compared control sabes (2 “Therefore improved understanding of etary impact on prevention anor outcomes of COPD may increase Sint and dial awareness about he importance of nuttioal approoches aswell, {5 provide directions for future research aed segs to promote lng health and prevent disease cnvet and progesion. "Thee i expanding literature on the topic regarding diel-COPD relation. A literature search performed with the PubMed database to deny papers with the folowing terms “let” and “chronic ‘Sbstractve pulmonary dleas sk” retrieved 233 manuscripts (rom 1989 to 2019). The resulted ‘manuscripts were analy using the informa dala analysis tool VOSwewe [2] which extract sand analyzes the words inthe les and abstracts ofthe pubiatons, eats them to ation cous and visualizes the results asa bubble or term map, based onthe strength of the coccurence inks ‘within the tems Te ers with greatest total nk strength were selected and highlighted bubble ‘Theanayss tures 750 wor, of which 127 met the threshold levels inimum number of ccurence ‘ofateem =5), As shown n Figur, dit hs been the foeus of evant scene tention and several ‘ofthe word retrieved from the analysis were connected dit, fering behaviors and pec ods ‘nd natriens (sits and vegetables, antondans nara fatty acids, mest procs) MURRENR some of the main key research categories that ave boen the attention focus inthe tpi diet and COPD risk, Figure 1. The bubble map vines 127 keywords extract rom published papers reed in PubMat under te serch ome “dt and “cn truce pulmonary dacs eben 1999 and 209. Babe sz nets the equa cerence of he wor wie ae cole ‘hater comesponds ast fos ltd words Tw Buble ete cer pony the to ‘rons had mow nut cossarence‘The present narmtive review almed a asessing the avalale evidence from observational and Intervention studies to summarize curent understanding ofthe associations between dietary paler, inva foods, nutrients nd lang fenton and prevention and improvements of COPD. The bene ‘of nutritional supplementation (ef, high protshigh energy) in undemourshed COPD subjects iebeyond the scope of the present review nthe readers ave mst to other papers on the top (oo [2.23] an eerences therein, 2. Pathophysiological Aspects in COPD ‘Several pathogenic proce are thought tobe involve in COPD development and progresion, inching eal andsytemiconidatve stress oxdantin exces compared withsntondantapoct) ndinflammatonreutophils macrophages eosinophils ytokines, chemokines, ecsanods, Tl ike receptors, acute phase protein), procalaboic tats, proteas/antiprotase imbalance, alteration of Immune responses and call proferation,apeptess, and cellule senescence, and remodeling of he salle compartment and lot of ela cl by emphysematous detrction of parenchyma ‘Oxidative tress may relly cause hang damage though modifeaton of DNA, lipids or proteins, ‘sella initiate cllular responses that con drve the inflammatory responce within the kg, leading ton tissue degradation (emphysema). Molecular switches triggering inammatory responses COPD involve the activation of redox-sensitive tanscription factors (eg, nuclear factor (NFB), indection of aslophogy ane unfolded protein response [4] kn patra, NF-eB plays» ruc role inthe chronic inflammatory response found in COPD, regulating the expression of genes for ronflammtry mediators ILI, 1 IL-8 MCP-1, Ta) and chemotactic factors, 117A ‘and MIP-a)inselved in triggering lung inition by inflammatory cel, thus ampliying oxidative Stress and inflammations wellas causing emphysema, ross of small alrways and remodeling of ‘way walls, ultimately impairing lung fancon. Indced, the numberof NF-cB-posive epithelial ‘ells and macrophages increased in smokers and COPD patients and corelaed with the degree of iefw limitation (25) ‘Although primarily afecting the lungs, COPD is associated with extrapulmonary (systemic) ‘manifestations suchas weight ss, malnuteitin, and skeletal muscle dysfunction, which contbute tothe morbidity, reduced quality of ie and, posably, mortality ofthis disease. Furthermore, other chronic seas (locale co-morbidiis), clung CVD and especialy coronary artery disease {CAD}, osteoporosis, metabolic syndrome, depresion, an lung cancer, eng, others are highly prevalent atiens with COPD, canbe considered par ofthe nenpulmnary sequel ofthe disease, ‘withthe low-grade yes inaraton playing dec role in thet pathogenes, and inpetanly Few randomized dietary ierventio as have been conducted. na small 12 week andomized tial including moderate-l-severe COPD patients complying with an intervention to increase fruit, intake, no improvement in airways or systemic infammation and oxidative ses markers was ‘observed although the follow-up might have Bee to short to observe any sigifcant ec "71 In COPD patients, I-week supplementation with betoot ie, a ater source of nates that improves mitochondrial respiration and energy production via nitric oxide formation, increased plasma nitrate levels and deceased dastalic bod pressure (mean difference 46 mmHg, 95% CEQ, 51,7 <5) without any fet on walking capacity, piyscal activity level, or oxygen consumption of submaximal exes [] However another randomized il reported tht COPD patients floeing 1 itch inf and vegetables >I portion /day) showed an annual increase in FEV compared with ‘he contol group following. re diet over 3 years (p= 0.03), after adjustment for physical activity, aleahol intake co-morbiiies and exacerbation frequency [5] Collectively, these observations suggest fruit and vegetable consumption 2s an impestant eterminant of pulmonary fureton and COPD risk. It should be noted that fresh fut intake ‘may be one comprnent ofan overall hath lifestyle, ncluding less smoking, more physical activity, Tow consumption of Wester foods (eg, meat and increased consumption of vgetables (5.5.9) and other not checked nutrients nay mediate the observed beneficial elles. Furthermore, assessment f Heed wie or exled beth conden bcmartes of endogenous oxidative strata geerally Tackng in most longitudes, hs imine possibly Yo more accurately elec subject more suscepsble to antioxidant dctary regimens and to appraise the antiondant efficacy of ested. foods over tine 6.2 Yamin and Nonlin Antoiants lnaible mechani ueetying frit ane vgeablepoiecive eects inca hr tenia and ant ivammatory activites a tagged by the epidemiologic atciaton aber tween Fit land vegetable consumption and lower markers of oxidative stes and infammation, and higher levels ‘of anioxsdant marker [5,,Frutsand vegetables beneficial fet on respiratory function may ‘be partially contbuted by their high content in vitamin and nonlin antioxidants. Accordingly, Ingher dietary intakes of vitamin C hydrophilic antonidant were ascites with higher levels of EVI [35/2] and witha lower ats of delne in FEVI afer year folow-p perio Other tas id not confiem a significant eco vitamin C dietary intake on lng faction FEV) ts longteinat ‘ecine [9], COPD incidence [52 or morality [5] Although not const [2, protective leas ‘heen died other veins such x wlan te ocopher pi soluble mnosdant ectingn “ynery ith vitamin Cand able of eskng lipid peroidation chain reaction and protecting the ing ‘again oxidative damage [3655], Lower serum vitamin E levels have ben cbserved in COPD ding ‘exacerbation compared to table condition [5] Randomized tris of vitamin E supplementation in linia populations have, however, reported mixed resus, incuding Both protective [6] and no ‘eft [3 on the rk of developing COPD.Butand etal. 1 found a positive ross-sectional association between higher consumption of ard fruits, suchas apples (5 or more apples per week) and lung futon (EVI) (138 mL higher FEVI for ‘hose eating Soe mor apples pr week compared with aonconsumer, 5% I-86, 2181, fr tad -180 gay), ‘wholegrains (245 gla, an leah (1-30 play) on FEV and COPD symptoms were ative {favorable vs. unfavorable intake, 19 ml higher FEVI and COPD symptoms prevalence OR = 04, -< O00 [1], suggesting important interaction among ateens and fod groups. Moreover ndings from the ECLIPSE stayin COPD subjects demonstrated that recent consumpson of "healthy fds, suchas fruits (grapetrltand banana) hea dary product and aloha was anocated wih higher ln fanction and le decline verte, es empyema and emphysema progression, ester mint \walkand St. George's Respiratory Questionnaire (SGRQ) scores, and lover levels of inflammatory markers (Creative protl, white Blood cell surfactant protein , total neutrophil) 101} These data extend the oe for dietary intakes to phenotypic feature of COPD pains 66. Yonin D Limited evidence also support a direct corration between vitamin D level, which mainly depen on sun exposure in addition to det and lung function, COPD incidence symptom, severty ‘and progression 102-104}. Genetic variants inthe vitamin D-binding protein associated with lower plasma vitamin D level have also bee nk to COPD ens. Mecniste tadis support role for vitamin D other than elem ffs ann partic in normal growth nd development of he hangs well asin immune responses and COPD progression. Vitamin D supplementation tril to prevent COPD exacerbation reported conflicting results bu, collectively, pointed to a benefit ony tn patients with low baseline vitamin D levels (2, levels of active metabolite 25-hydroxyvitarin D 25 nmol 05. Although further studis are needed, aking into account the igh prevalent ‘xteopoens and risk of fale in COPD paints and also te supposed benef effects of vita D ‘beyond bone health screening for vitamin D deficiency (25 hydronyitamin D 5 times/week) ‘vas sigaiscanlycoralated 4 chronic bronchitis in US adults (OR = 180, 98% CL 101,320, (0047 {1}, as well as to pediatric asthma [55], possibly due to the formation of AGES from the interaction betwen unabsorbed fre fructose an dietary proteins the gastrointestinal tract. These ‘sults erly emphasize the public health implication of interventions targeting modem unhealthy syle habits 7. Dietary Fates, Lung Function and COPD Dietary patterns have been widely investigate in ation to cance, CVD or eabtes 2h, but limited data are avaable o their association with respiratory outcomes with relevance to COPD. ‘As shonin recent meta analysis} most studios were perlormed in Europe and Novth Ameri, luting the generalizability of tadySndings, and were nervatonal in design Overall the evidence ‘concordant scat that the pater of distor intake ean importa fctorin the pathogenesis and prevention of COPD and provided sspport for specific ietary modifications as lnc relevant tool to promote ung health Moreover examination of dietary patterns complements the evaluation of the ffs of individual ood and natin intake on COPD. Table | summarizes findings fom main pidemiolgia studis addressing the relation between dt and lang function, COPD risk sympa, snd progrnion“be 1 Main fading om epieinoga stds inking dear pater toadlt ang fncton and hensive play disease (COPD) dens, prevalence ac every) Dina Egil) Pein Sathya Oates Sa, Mesto ue ee ee ne wane Storms Titaccon ee Veet antag My” aan comin Siwenguscemsceseer tae eeereenerees ee ao es eee ee SELES SS lana Fon) mom cominiine stoped samme Depo pee ne pt oad — SR Soham Rc RE eee nomic SER? gemmay MEM eeRNS r a a Save eRe cy poe mas eee oan 7 ONE Sp en Stn mane “Tegan pi od SRSEED ity ee RT reeern SEES nmey TAGSspan ant resp hi i a corre Bina ‘iene some rete COPD aver ge Oe Sot ragh OR = 132, 98% CE 130 15),p= Teme eae iaeren ena poe er Sieber mentee Gaetano feces Patent iene ae SEsone eee aoe es eerie (NHSand (iby NHS 12 ph, FOSS T= quay mex CORDincidence —Settreporms “Sth Ener CORD ok tr eur of is in St eg eta “SIT” pas eae ae SEIS cm EM ee conan cpa AMET, ay mote gly wy “HRI meme ES omy gta, “3 those “Riera: A = as Hay ag ne ARC — aden an oman C= mre CAD ala andes nara aly ctr IE = Rely xn ne FS ls Pes Play heed ERAS dee ‘etinermeom MORCENEFIC = Nn Pret Risk acs and Chic Discs nthe Nehsando-Fampean Penpecivinvesgton ns ance and Narn, NES ‘ip Hay = no sgan Os P psc PCA = prance ania R= mat i SAPALDO™ Sa hoa A ‘Suingun et uous ates = Sngapre Chae lh St7.1 Data-Driven DicaryPatens an COPD A cohort stdin Chines Singaporeans found that he met dim sum dietary pate (ed mist, preserved foots ce, noodles, deep-fried fod) was associated with an increased incident cough ith phlegm (ods ratio (OR) » 143 comparing fourth to fist quartile p for tend» 02) (146, Indicating a deleterious ect of dit rich in meat, starchy foods, and high-fat dairy products on respratory symptoms. Two prospective studies in US health professionals identified to distin ‘aor ditary pater, the“prodent pattern lndedby ahh nak fruits and vegetable oly fh, ose, wholegrain products, and neat ry prodctand the “Wester pattern” characerized by ‘thigh consumption f refined grains, cured and red meats, dese French res an hgh a airy products [117], Boh studies consistently found thatthe “prudent” pater was negatively and the Wester pater posivelyasocated with thers of elrported newly diagnesed COPD in ‘women [0] and men [107] ater adjustment or several potential confounders inclding measures af tcoeco exposures, In contrast wth findings for COPD, the dietary patterns wer not associated with therisk of adultenset asthma, Notably the ef ofeach etary pattern was stronger in men than in women [47,8 Foe the prudent patter, the relative risk (RR for highest vs. lowest quintle was (050(9 for tend = 002) inthe men cohort] and 075 (fr wend = {2 in the women cabot [1] Forthe Wester patter the Ki er highest vs. lowest quinle was 436 (fr rend 015), suggesting that may protect lung fartion agains he deleterious lca toking [11 “The study By Sorl-Agailar ta. [50] provides some new information: (1) resrcted the ‘bservatonto smokers, thus stressing the importance of eating pate, ination to smoking cessation, asapossblepreventivemeasureforimpeovinglung beat 2) poviesafistreprtontheassocation between a Mediteraneanlike dit and lung function, An impressive and unprecedented acral of ‘high-quality evidence fre servations and inierventional studies converges tothe rexogition of ‘he tational Meiterancan dita one ofthe healthiest dietary pattems, being protective against incidence and morality of major chronic diseases, mainly CVD and cancer (197,58), However, limited evidence exists for aoe in obstructive espratory diseases and mostly regards asthma [9 ‘As discussed above man individual fods and nuteiens characteristic the Medterzanean diet and ‘endowed with ntinlammatory aninidant and benef mctabolic properties (ai vegetables, ‘seafood nts legumes vitamins polyphenols et) have been ascites to improved ang fanton nd COPD preventionin several ies The Mditeraneanlik diet pattern described by Sor Aguiar ‘eta, the heltest one compared tothe other dietary patems identified, included hey fods ofthe traiional Mediterranean it (ul, vegetables, legumes, wholegrains, ats, lve ol sh) [10] and ‘assim to the ‘pradert” ptr that have ben previously found wo proect again imped lang function and COPD is [165] However tannot bestrly defined aa tracittonal Mesterancan it because tao included non Mesiteraneandieuhalthy components, such sed and processed reat, deserts, sweets, and refined gas [15]. Tals may have diluted or masked the possible postive ef on lung faction by ater beneficial components, Of course mor vestigations (nosy [etervenionalin dexiga) in diferent popultons and counties ae rend to crf Mediereneen ‘Set health beefitsin COPD. 7.2, Det Quality Seo end COPD Inadaition to data-driven approaches to deriv tary pater, a pie -etned det ual sores havealso been set assess andlor confi the elaonship of diet wit lang fanction and risk ne ‘outcomes of COPD (Table) In ade o measure compliance tthe Dietary Gielines for Americans (GAs) and provide dietary guidance for healthy eating, two dietary nies, the Healthy Eating Index (GE [16] andthe Alternate Healthy Eating nex (AHEE (2005 ana 2010 eons) [62a modified ‘version af the HEL have been developed and used inthe US population and subpopulations. Apart from some distinctive feature, such as mor attention to fat quality inclusion of moderate all intake cereale red-to-white met rai, and duration of multi wen the AHEL compared 9the orginal HEL both scores reflect dietary pattem characterized by high intakes of wholegrain, PUFAs ts and long-chain 3 fats and low intakes ofred/processed meats, refine grains and sugar sweetened beverage, and have been fund to beneficially impact health outcomes. Indeed, the ‘AHL was inversely saociated with incidence and mortality rom chronic daeses (CVD, diabetes, ‘and cancer) [8 16s. Using the AHEL2010 score a recent several year ang prospective sd in participants ofthe US Nurses’ Health Study (NHS, » = 7300 women) and Health Professionals Follow-up Study (HPS » = 4700 men [5] found that higher AHEL-2010 diet score was associated ‘wih a 3% ower risk of newly diggnased COPD in both men and women, without any effets by tsmoking lates and afieradjuient for several codounding factor (omlivansble HR for eating the bealthet dct compared to eting the leat althy diet = D67p fr tend .01), This negative association also persisted after excuing participants wth cancer and CVD at baseline (multivariable HR for eating the healtest det compared with eating the least ealthy det = 071, p for tend 0007), indenting a dct eet ofa healthy det on COPD beyond ts asselation with her cone senses. Conary, noasscition 3 found between AF and the risk of at ons asthms, “Although obtained in sth profesional with differences in heath awarenes, ecosconomic st, land smoking behavior compared tothe general population thee rests extend the relevance ofthe ‘AHTEL2O10 det score and its main etary features to COPD. When the association between invidual components of the scot and the rk of COPD wa analyzed, high intake of rule and wholegrain and leet fred and proceed mest nd sugar rested drink andr jue were sence wth lower sk of COPD [5], confirming some previous nang about the spray Benet of lst ‘itary pattems, nagreement with the anoxidant and antinlmimatory det hypothesis [85,11 Another more recent study sed the HEI 205 and 2010 editons) diet scoreande medi version ‘ofthe Mediteranean diet coe [65] assess the erosectonal association ofthese wo det quality scores with COPD severity (according t» GOLD stages) and parameter of lng function (FEVI and VC) in 121 patients with tale COPD [155),Both cores reflected high intakes of fruits vegetable, ‘wholerains, PUFAS,MUEA, nut, legumes, and low intakes of veined rains redcured meat (andre ‘meat to white mat aio), sturatd fat empty calris and sodium. In parcul the Meiteranean ‘et score, fom it orginal conception [6s] the latest mowifcaons [65], inended to captre ‘compliance tothe pleni-bsed eating plies live bee rowing ret of he Medinronean bn. ‘According to both HET and Miterrancan diet scores, the diet quality ofthe study subject appeared ‘to nee improvements. Although not reaching significance, reduced HET and Mediterranean cit scores wer observed with nereased COPD seventy, mostly lage 4 and a oneunit increase ofthe Mediterranean det score was sigan associated with (=O 002) and'28 (= 0.107 increase of FEV and FVC, respectively [155]. Although obtained na small sample already diseased sujet, these ssels farther suggest protactve elects on hg function by He Meditercarean diet pater. Further high powered confirmatory stdiesas wellas the evaluation of defect on COPD progression ‘overtime are highly warranted Inavery recent rosesectional study conducted in midlet healthy subjects atowtomoderste (C¥ sak but without pulmonary dents (emda Vascular Project, ILERVAS [55], low adherence to the Mediterranean diet as well lowe physical activity practice were independently associate ‘sith the prsence of impaired spirometric values and wth ventilatory defects compared with high lacherence tothe Mediterranean diet and vigorots physical activity. ‘Therefore, although we are stl awaiting interventional studies providing causality, these results agree with hase previously ‘binned with dietary pater aly [155] wel colletvey suggest aber mocaion bebe the Meditsenen dc nd ang fection with relevance tooth the prevention of renpirtony diss {as ll asthe improvement of COPD, Ina large prospective Aslan cohort study adherence to several recommended dietary pattems as reflected inthe AHE-2010 the allerate Mediteranean dit score, the dietary approaches stop Inypertenion (DASH) sor, and the healthy dit indicator (HDI, and based an healthy plant-based foods and fh, was associated with a substantially lower sk of 17-year allcause and dstase specific(CVD, cancer and respiratory disease) mortality, specifically with 14-28% ower rskof morality for respratory diseases [167 Interestingly, COPD was one ofthe predominant espiratory conditions ‘ontibuingto reapistry diseae morality in the sod cohort. These renuls agee with esi ‘ports ofan inven anciion beeen nia of ingle Eicterycomponnds of thea cary pater, ‘ichas fits and COPD morality (5) Other ste in ferent populations confirmed the benef {sociation betwen adherence to the DASH diet and COPD risk [and adherence tthe healthy Dutch dietary guideline and the sk ofal-cuse morality and COPD development [6 Collectiely, although needing further confirmations, published studies concordanly suggest «sigan ole foe haghrquaily whole dit on lang fancion eufcomes end CORD inches aed revelenc, walls om moray. Adhering to dic peti resembling the general princes of the Mediterranean diet and the prdent iets, which emphasize a variety of heathy pant bas foods (egetbls, rut nuts, wholegrain) ands avokdance of hea alcool intake and low owsumption ‘of foods typical of Westemized patterns (ed/processed meat, refined grain, sweetsiessers), exerts ‘bene fet conrast with Western des Figure). Interestingly the Wester diet has ben shown to be positively associated while the prudentMediterranean diet inversely associated with serum levels of namatory markers [17,171 Moreover, beneficial fects have also been documented for bioactive nutrients ofthe heathy diets suchas polyphenol and PUFAS, aint viseral adiposity and related inammaton/xidaive stress, mtochondeal dysfunction, a well as insulin resistance [172] thus potentially providing the opportunity to fares menage the Hak msocialed with metabolic _derangements observed in some patients with COPD obesity andor abdominal vnceral adiposity ss Fras segeabes whale (palm echoing len a ak Highs iw anata tow emsine twtr Urata OA, igh eeemicinde MURA} ‘Sitar Seton sept ay ‘estaba, oy # Disste ptbgznsia Figure A fumeworknel othe inact de ar try facee wih ng fotion and (COPD devopment and prgrein. In ation to direc improving ifamimation, oxidative tes, and immune and metabolic deregulation star factors wy acy icucing enifestion of gut miccbit, which can infecImmune sytem, system infammation, and metabolism through the production of lca and ystemiclly-cive metabolites, such asthe fiber fermentation derived shat chain fat acid (SCFAS) (Galyrate, propionate and acetate) or the caitinecholine- derived rimehylamine-N-oxide (TMAO), Human suds have found tht plantbaed diets such asthe Mediterranean dic (ich infer) shaped the compostion of gut miei 935 9 increase the cculatng Ives of nsinflammatory SCF, ‘while aimal-baod iets such asthe Westem dit (ich in cain ane choline from meat e8YoKS, land high-fat dary products) were associated with increased levels of he pro-ilammatory TMA, Ishich ikea tsk of ehorosclerosi, CV disorder, and marty [175]. An emerging concept ‘hd potential therapeutic opportunity for detary modulations the gut-lang ai, where intestinal ‘lcrbil modulation can inuence the reapieatry syst [17]. Indeed, high dietary be intake ‘was show to protect against ilammatory airways disease va systemic SCFAS [175]. Moreover, Increased cclating TMAO levels were associated with longer al-case moray inpatients with COPD [176 Ofcourse further stadies are quired adress whether gu-lung als modulation by ution would beefy impact ang neon andthe isk or evlton of COPD. |. Conclusions and Perspectives Give the alarming increasing bunten of COPD worldwide, dentition of modifiable isk ‘actors for prevention and weatment of COPD ishighly in demand, Based on the avaable evidence, (eter ewvurenan of dct end istry factors inftvencing repay health may be of interest or ‘ublic health duc to their cease modifying effcts. Many readies nthe general population and in subject with respiratory disease have reported that current dietary habits are qualitatively poor and therefore leave plenty of opportunites fr improvements and interventions. Taking ino account the increasing smoking habit in developing countries and the worlwide unstoppable phenomenn, ‘of Westemization of esl actos, including a more processed and conventnce-orentte dit, {tnt dye ben (olin are unhealthy det curendly ing, Based on strong evidence of association with improved cardiometabolc health, including lower sk of CV disease, diabetes, and obesity, many scentfe organizations recommend the pradenyMediteranean-ie diets a healthy dietary patterns. Published studies also consistently how ‘he adverse effets of the Wester de chin fined foods, saturated fa meat, and Sugar, om ng, fanetion andthe risk of COPD, and by contra, he abit of spi dtary factors and des, mo the pracnt/Mediterranearlike diets loaded by plant-based foods ant heathy fast preserve hing, function and prevent COPD or itsevoltion over time Interestingly the magnitude of efecto et ‘on lung function is eatimated to be comparable fo that of one smoking [51], underscoring that Inaliydctry eppreches my haven ges impetontly on COPD developenent ad the enociaed Interestingly many suds specie distr pattems andor nutrient exerted benefits on ing, function and the sk of COPD, but nat astna strongly suggesting a rue underlying fet ater han ‘generalized and mos! probably confounded effect. COPD as wellas CV diseases share systemic Infaamaory pathogenesia diferent fron the irumune pathogenesis of eth. Nutritional arpatng ‘fondle balance acd oveshelnngifleunation my terfoe represen nique epportriy 62 roveneat COPD and its elated CV comorbites. ‘OF course, thee isnot a single det Kentified as 9 magi pil for resptstory health. Food groups, cluding fats, vegetables, sh, and wholygran products contributing to base ntraceutal Ingredients, such a antonidans, vitamins, fiber and PURAS, may vary across the dietary patterns documented to be beneficial for ling function, according # the populations sted. However, some uityng principles fal th helt diets maybe recognized and emphasized in designing Preventive nutitional measures, In many studies dietary factors documented to improve seve processes (nlarmatin, oxidative stress a immune dysfunction) and co>-morbidies (CVD, obs) of respiratory diseases warslat into improved respiratory outcomes. Inpartanly, considering the txry origin of COPD [10] and the profound inpet of dit on lung ction and later repiatry‘neath, rutton intervention offers the opportunity fr carly strategies of primary prevention andlor targeted early therapeutic approaches. “The nogative ule of supplementation ral with single antonantmutint sugges thatthe ic of snp natin ay be too mall tobe chacrved,renoreing the tion that ombanation of ‘trent an fonds wethina dietary pate may allow cmultivesymegiceets o bcome apparent Moreover, since et testo tack throughout if, this means that exposure to or lack of certain nutrients may occur over lng period of tine (a capture in cbservationa studies). Therefore, boervational studi of dietary beneits may not alway translate int postive results rr clinical ‘els (peformed in a ope age group with singe netinls nd for aie alow-iph. ‘With gard to dncase weatment several therapeutic strategie sncluding smoking cettation, ‘Pharmacological interventions and rehabilitation programs, are implemented in COPD patients to improve quay of fe, decelerate lung function deine, and prevent major complications ‘As malntation associated with skeletal muscle implements an important systemic and isabling ‘omsequene of COPD, nutritional support (eg, enegy-enriched dit) hasbeen recently supe 1358 valuable adjavant tol inthe management of COPD patients at risk of malateton, mainly in combination with physical exercise [171 suggesting tha at least some ofthe adverse functional ‘consequences of severe COPD are reversible by national suppor [2 More anal experimentatons and human intervention studies are needed to confirm the iectvenca end reteniseso ditin preventing end testing COPD. A new are of ivesigaton isthe micmbita modulation by dict, which afer the prospect of increasing eslth and mitigating disease sk, Howover, the field of nutigenetics (ie, the relationship betveen genetic variants land diet) alo deserves attention to addres the interindividual variably in rexponse to dst and Improve personalized nuttin intervention to preventeat COPD. Moreover, is possible that dict inluences enay be different acre diferent cial phenotypes of COPD, os somne evidence ‘suggests [101]. Therefore, more studies are needed to ascertain the eft of dit on iferent COPD ‘Phenotypes and to develop tailored nutritional statgis. Although evidence forthe role of dietin ‘COPD is clear avalabl, smoking cessation and the appropriate pharmacologic therapy remain Key rmetsues forthe prevention and tatiment of COPD. ‘Although cument murtonal guideline for COPD management do nt formally nce pectic “Setar recommendations ther han national counseling for malnourished patients, he available ‘sien evidence provides new dretons for fature research to substantiate the role of matron in Tang funtion maintenance, respsatory disease prevention, and teatment, lading tothe ultimate positioning of ution on the rd to optimal repeater health Based on the evidence presented inthis veview ae pending further evidence from base since and interventional studies, «pragmatic view for managing apiratory heals and COPD, aswell ‘asmany other aspects of health, would be to recommend (long with physica eerie) a healthy ‘balanced dot characterized by high consumption of fesh ris, vegetables, wholerans, plant ols and sh, low inlake falco (preferably wine), and avoidance of processed fined high soturated fat foods, sweets, cured mest and nagar conning beverages ‘Most importantly arrent ies there maybe 3 wide range of appropriate approaches to diet that shouldbe considered and incude soca cltral, and paychologcl aspects of eating. Morover, -uteton-based measure for ealth maintenance and diese management are complicated hy ieee such food production and procesing technologies that need careful attention and convergent efits ‘by health policy maker, the fod industry, health professionals, and consumer in oder align ‘sonal heath elas with sustsinable fod eye. All hea oasidesions end echievemesia ‘have the great potential to improve evidence-based public helth recommendations fra heathicr eating pattern to adopt ety in ie as arto heathy hfestyen onde to preserve lung function and prevent or improve COPD, inadkiton to encouraging smoking avdanceor cessation, and especially Inamokers who ar unable to qui smokingAuthor Contsbulions Conception, ES. and DST; nvetipton ES and MLM. wing dt ‘Papurton ES wens nek an dling Sand DALT supers Sand DLT Funding: Tic eeach ccived oeterma fading ‘Conic of nee The authors dace no ini finest References 1, Adloe, Chun S; Le, C; Bsqul,C; Papa, A; Theodore, Ej Nal, Gasev D Sea Dy Campo eta. ltl and repona estimates COPD preven: Syma rev and melanie Gh Het 235, 500015, [mat Pues} 2. Barns, Pf Supt, SD; Pauwels R.A Cone cstructve pulmonary disease Molla ese mechan at ir | 20, 2, 47-486 [oc Po 1. Wen Js Hn S87 Agi A. Jones, PW: Veiner C: Anzu, A; Bares, FJ: Fabio LM Masinz fz Nshimery Me a. 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