{"id":5982,"date":"2026-10-19T09:48:18","date_gmt":"2026-10-19T09:48:18","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-jon-petur-joelsson\/"},"modified":"2026-10-19T09:48:18","modified_gmt":"2026-10-19T09:48:18","slug":"doktorsvorn-i-lif-og-laeknavisindum-jon-petur-joelsson","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-jon-petur-joelsson\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – J\u00f3n P\u00e9tur J\u00f3elsson"},"content":{"rendered":"
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Mi\u00f0vikudaginn 24. j\u00fan\u00ed ver J\u00f3n P\u00e9tur J\u00f3elsson \u00a0doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. V\u00f6rninni ver\u00f0ur streymt:\u00a0https:\/\/livestream.com\/hi\/jonpetur<\/a><\/p>\n

Ritger\u00f0in ber heiti\u00f0: \u00der\u00f3un frumul\u00edkans fyrir \u00feekjubrest af v\u00f6ldum \u00e1lags vi\u00f0 \u00f6ndunarv\u00e9larme\u00f0fer\u00f0: Hlutverk azithromycin sem \u00f3n\u00e6misbreytandi og \u00feekjustyrkjandi lyfs. Modeling ventilator-induced lung injury in vitro: Emerging role of azithromycin as an immunomodulatory and barrier enhancing drug.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. Jin-Ah Park, d\u00f3sent vi\u00f0 Harvard T.H. Chan School of Public Health \u00ed Bandar\u00edkjunum, og dr. Sif Hansd\u00f3ttir, yfirl\u00e6knir lungnal\u00e6kninga \u00e1 lungnal\u00e6kningadeild LSH.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var dr. \u00de\u00f3rarinn Gu\u00f0j\u00f3nsson og me\u00f0lei\u00f0beinendur voru Gu\u00f0mundur Hrafn Gu\u00f0mundsson pr\u00f3fessor og Sigurbergur K\u00e1rason d\u00f3sent. Auk \u00feeirra \u00ed doktorsnefnd var Margr\u00e9t Helga \u00d6gmundsd\u00f3ttir d\u00f3sent.<\/p>\n

Engilbert Sigur\u00f0sson, pr\u00f3fessor og forseti L\u00e6knadeildar H\u00e1sk\u00f3la \u00cdslands, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13:30<\/strong>.\u00a0<\/p>\n

\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n

Me\u00f0fer\u00f0 \u00ed \u00f6ndunarv\u00e9l er l\u00edfsbjargandi fyrir alvarlega veika sj\u00faklinga \u00e1 gj\u00f6rg\u00e6sludeildum \u00fear sem tekin er yfir vinna vi\u00f0 \u00f6ndun og stutt vi\u00f0 loftskipti \u00ed lungum. \u00d6ndunarv\u00e9larme\u00f0fer\u00f0 getur hinsvegar leitt til skemmda \u00e1 \u00f6ndunar\u00feekju vegna \u00fer\u00fdstings- og slit\u00e1lags. \u00deetta er \u00feekkt sem \u00f6ndunarv\u00e9latengdur lungnaska\u00f0i (\u00d6TL) (e. ventilator-induced lung injury, VILI). Allir sj\u00faklingar sem f\u00e1 me\u00f0fer\u00f0 \u00ed \u00f6ndunarv\u00e9l eiga \u00e1 h\u00e6ttu a\u00f0 f\u00e1 \u00d6TL, s\u00e9rstaklega \u00feegar \u00f6ndunarv\u00e9larme\u00f0fer\u00f0 ver\u00f0ur vandas\u00f6m s\u00f6kum sj\u00fakd\u00f3ma \u00ed lungnavef, eins og \u00feekkt er me\u00f0 br\u00e1tt andnau\u00f0arheilkenni (BAH) (e. acute respiratory distress syndrome, ARDS). \u00d6ndunarv\u00e9larme\u00f0fer\u00f0 getur \u00feannig auki\u00f0 vi\u00f0 alvarleika BAH og framkalla\u00f0\u00a0 frekari skemmdir \u00e1 \u00f6ndunar\u00feekjunni, en er um lei\u00f0 nau\u00f0synlegt me\u00f0fer\u00f0ar\u00farr\u00e6\u00f0i. Ranns\u00f3knir \u00e1 BAH og \u00d6TL eru erfi\u00f0ar vegna \u00feess hve alvarlega veikir og vi\u00f0kv\u00e6mir sj\u00faklingarnir eru. Nau\u00f0synlegt er a\u00f0 finna og skilgreina \u00e1rei\u00f0anleg l\u00edfmerki (e. biomarkers) til a\u00f0 greina tilur\u00f0 og fylgja eftir \u00fer\u00f3un BAH og \u00d6TL. Notkun \u00e1 in vitro l\u00edk\u00f6num til a\u00f0 rannsaka BAH\/\u00d6TL hefur lofa\u00f0 g\u00f3\u00f0u en t\u00e6ki sem getur framkalla\u00f0 \u00fer\u00fdstibylgju (e. cyclical pressure) \u00e1 frumur r\u00e6kta\u00f0ar vi\u00f0 loft-v\u00f6kva millifasa (LVM) (e. air-liquid interfase, ALI), l\u00edkt og gerist vi\u00f0 \u00f6ndunarv\u00e9larme\u00f0fer\u00f0, hefur ekki veri\u00f0 til. Vi\u00f0 LVM kringumst\u00e6\u00f0ur mynda frumurnar s\u00e9rh\u00e6f\u00f0a og skauta\u00f0a \u00feekju sem er mun l\u00edkari \u00fev\u00ed sem gerist \u00ed lungum \u00ed sta\u00f0 einfrumu \u00feekjulaga (e. monolayer) sem jafnan hafa veri\u00f0 nota\u00f0ar vi\u00f0 sl\u00edkar ranns\u00f3knir.<\/p>\n

Markmi\u00f0 \u00feessa doktorsverkefnis var a\u00f0 hanna og sm\u00ed\u00f0a t\u00e6ki sem g\u00e6ti framkalla\u00f0 \u00fer\u00fdstibylgju l\u00edkt og vi\u00f0 \u00f6ndunarv\u00e9larme\u00f0fer\u00f0 yfir frumur\u00e6kt \u00ed LVM kringumst\u00e6\u00f0um. Jafnframt var markmi\u00f0i\u00f0 a\u00f0 rannsaka \u00feekjustyrkjandi og \u00f3n\u00e6misbreytandi \u00e1hrif s\u00fdklalyfsins azithromycin (AZM) \u00ed LVM, me\u00f0 og \u00e1n \u00fer\u00fdstibylgju \u00e1lagi. AZM er brei\u00f0virkt s\u00fdklalyf sem algengt er a\u00f0 nota vi\u00f0 \u00f6ndunarf\u00e6ras\u00fdkingar. \u00deekkt er a\u00f0 AZM hefur \u00e1hrif til bata langvinnra lungnasj\u00fakd\u00f3ma en \u00feau \u00e1hrif tengjast ekki s\u00fdklalyfjavirkni lyfsins en langt\u00edmanotkun \u00feess getur hinsvegar leitt til s\u00fdklalyfja\u00f3n\u00e6mis \u00ed bakter\u00edustofnum. Ranns\u00f3knarstofa okkar hefur \u00e1\u00f0ur s\u00fdnt fram \u00e1 \u00feekjustyrkjandi \u00e1hrif AZM.<\/p>\n

\u00cd \u00feessu verkefni var hanna\u00f0 og sm\u00ed\u00f0a\u00f0 t\u00e6ki (e. cyclical pressure air-liquid interfase device, CPAD) sem getur framkalla\u00f0 \u00fer\u00fdstibylgju yfir LVM r\u00e6kta\u00f0ar lungnafrumur og \u00feannig l\u00edkt eftir \u00fev\u00ed sem gerist vi\u00f0 \u00d6TL \u00ed in vitro l\u00edkani. S\u00fdnt er fram \u00e1 a\u00f0 sl\u00edk \u00fer\u00fdstibylgja veldur \u00f6flugu \u00f3n\u00e6misvi\u00f0brag\u00f0i og \u00feekjubrest LVM r\u00e6kta\u00f0rar lungna\u00feekju. Einnig er s\u00fdnt fram \u00e1 a\u00f0 me\u00f0h\u00f6ndlun lungna\u00feekjunnar me\u00f0 AZM lei\u00f0ir til h\u00fa\u00f0\u00feekjutengdrar frumus\u00e9rh\u00e6fingar me\u00f0 upps\u00f6fnun bla\u00f0ra og lamellar korna (e. lamellar bodies, LBs) \u00e1samt breytingum \u00e1 l\u00edp\u00ed\u00f0b\u00faskap frumnanna. A\u00f0 lokum er s\u00fdnt fram \u00e1 a\u00f0 lungna\u00feekja sem f\u00e9kk me\u00f0h\u00f6ndlun me\u00f0 AZM \u00feoldi betur\u00a0 \u00fer\u00fdsti\u00e1lag \u00ed CPAD me\u00f0 vi\u00f0haldi \u00e1 reglulegri uppr\u00f6\u00f0un akt\u00edn \u00fer\u00e1\u00f0a sem myndu\u00f0u \u00f3rei\u00f0u \u00ed \u00f3me\u00f0h\u00f6ndla\u00f0ri lungna\u00feekju. AZM me\u00f0h\u00f6ndlun dr\u00f3 einnig \u00far \u00f3n\u00e6misvi\u00f0brag\u00f0i \u00ed lungna\u00feekjum sem ur\u00f0u fyrir CPAD \u00fer\u00fdsti\u00e1lagsme\u00f0fer\u00f0.<\/p>\n

Samanteki\u00f0 hef \u00e9g s\u00fdnt fram \u00e1 a\u00f0 n\u00fdtt t\u00e6ki, sem l\u00edkir eftir \u00e1hrifum \u00f6ndunarv\u00e9larme\u00f0fer\u00f0ar, getur framkalla\u00f0 \u00fer\u00fdstibylgju yfir lungnafrumur \u00ed LVM in vitro og leitt til vefjaskemmda l\u00edkt og vi\u00f0 \u00d6TL. \u00deetta hefur gefi\u00f0 okkur t\u00e6kif\u00e6ri til a\u00f0 rannsaka \u00e1hrif AZM til a\u00f0 draga \u00far sl\u00edkum skemmdum\u00a0 me\u00f0 \u00feekjustyrkjandi eiginleikum og dempun \u00e1 \u00f3n\u00e6misvi\u00f0brag\u00f0i. \u00deessi vinna s\u00fdnir fram \u00e1 frekari \u00fe\u00f6rf \u00e1 ranns\u00f3knum \u00e1 AZM og styrkir \u00fe\u00e1 hugmynd a\u00f0 rannsaka lyfjaaflei\u00f0ur AZM sem hafa ekki s\u00fdkladrepandi eiginleika en geta m\u00f6gulega dregi\u00f0 \u00far e\u00f0a hindra\u00f0 \u00feekjubrest.<\/p>\n

Abstract<\/strong><\/p>\n

Mechanical ventilation (MV) is a life-saving therapy for critically ill patients, alleviating the work of breathing and supporting adequate gas exchange. However, mechanical ventilation can be injurious to lung tissues by mechanical stress through baro\/volu- and atelectrauma and by oxidative stress through high fraction of oxygen in inspired air, collectively called ventilator induced lung injury (VILI). All mechanically ventilated patients are at risk for VILI, especially when it becomes challenging to ventilate the patient due to pathology in the lungs, as in acute respiratory distress syndrome (ARDS). MV can thereby cause, or augment substantially, damage of lung tissue in ARDS while being a necessary part of its treatment. The study of ARDS\/VILI is hampered by risks in obtaining samples from patients for detailed studies but there is a need for reliable biomarkers. Using in vitro models to study ARDS\/VILI has been promising but there has been a lack of a device capable of cyclically stressing air-liquid interfase (ALI) cultured lung cell layers mimicking effects of actual ventilator therapy.<\/p>\n

The aim of this PhD project was to design and make a device capable of cyclically stressing ALI cultured lung cells, mimicking the effects of VILI. I also wanted to further explore the epithelial barrier enhancing and immunomodulatory effects of azithromycin (AZM) on lung cells. AZM is a commonly used broad spectrum antibiotic. Our laboratory has shown that AZM has barrier enhancing capabilities and it is recognized that AZM has disease-modifying effects not related to its antibacterial effects, leading to reduction in exacerbation of chronic airway diseases. Although inflammation is a necessary protective mechanism of the human body, excessive inflammatory responses can be detrimental. There is concern regarding the use of antibiotics as maintenance therapy of chronic airway diseases as there is a high correlation to antibiotic resistance.<\/p>\n

In my work, I have designed and produced a cyclical pressure air-liquid interfase device (CPAD), capable of cyclically stressing lung cell layers, mimicking VILI conditions in vitro. I have shown that by mechanically stressing the cells in the CPAD there is a robust inflammatory response and a disruption in the barrier integrity of the cell layer. I have also shown that AZM treatment induces epidermal differentiation in lung epithelial cells. Further, an accumulation of multivesicular and lamellar bodies (MVBs and LBs respectively) was observed as a result of AZM treatment along with changes to intracellular lipid dynamics in cell models. Finally, the work presented in this thesis displays that pre-treatment of bronchial and alveolar cells cultured in ALI with AZM results in barrier protection when cells are mechanically stressed in the CPAD, evidenced by maintenance of actin structures of the cell layer, otherwise compromised in the untreated layers. AZM pre-treatment also results in attenuated inflammatory responses in mechanically stressed cell layers.<\/p>\n

Collectively, my data presents a novel method for cyclically challenging lung cells in vitro and the robust effects of AZM in attenuating lung injury by way of barrier protection and a reduction of excessive inflammatory responses. This work highlights the need for further exploration of AZM and supports the notion of researching non-antibacterial derivatives of AZM.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

J\u00f3n P\u00e9tur J\u00f3elsson er f\u00e6ddur \u00ed Reykjav\u00edk \u00e1ri\u00f0 1978. Hann lauk st\u00fadentspr\u00f3fi fr\u00e1 Fj\u00f6lbrautask\u00f3lanum \u00ed Gar\u00f0ab\u00e6 \u00e1ri\u00f0 2000, sveinspr\u00f3fi \u00ed rafvirkjun fr\u00e1 Fj\u00f6lbrautask\u00f3lanum \u00ed Brei\u00f0holti \u00e1ri\u00f0 2006, BSc-gr\u00e1\u00f0u \u00ed l\u00edft\u00e6kni \u00e1ri\u00f0 2013 fr\u00e1 H\u00e1sk\u00f3lanum \u00e1 Akureyri og MSc-gr\u00e1\u00f0u \u00ed l\u00edft\u00e6kni \u00e1ri\u00f0 2015 fr\u00e1 NTNU \u00ed Noregi. J\u00f3n P\u00e9tur hefur samhli\u00f0a n\u00e1minu starfa\u00f0 sem s\u00e9rfr\u00e6\u00f0ingur hj\u00e1 EpiEndo Pharmaceuticals og sinnt kennslu nemenda vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Fa\u00f0ir J\u00f3ns P\u00e9turs er J\u00f3el Fr. J\u00f3nsson og m\u00f3\u00f0ir var \u00de\u00f3ra \u00d3lafsd\u00f3ttir. J\u00f3n P\u00e9tur \u00e1 d\u00e6turnar Freyju, 10 \u00e1ra, og I\u00f0unni, 9 \u00e1ra.<\/p>\n<\/div><\/div>","protected":false},"featured_media":1172,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2020-06-24T13:30:00+00:00","_phd_date_end":"2020-06-24T16:30:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"\u00der\u00f3un frumul\u00edkans fyrir \u00feekjubrest af v\u00f6ldum \u00e1lags vi\u00f0 \u00f6ndunarv\u00e9larme\u00f0fer\u00f0: Hlutverk azithromycin sem \u00f3n\u00e6misbreytandi og \u00feekjustyrkjandi lyfs. 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