The Appropriate Use of Inhalers and Asthma Control

ma je kronična upalna bolest dišnih putova, čije se liječenje bazira ponajprije na primjeni inhalatorne terapije. Unatoč efikasnoj inhalatornoj terapiji problem kontrole astme kod velikog dijela bolesnika još je prisutan. Uzroci loše kontrole astme jesu brojni, međutim jedan od najvažnijih uzroka svakako je loša edukacija bolesnika i loša inhalatorna tehnika. U liječenju astme rabe se dvije velike skupine inhalera: DPI (dry powder inhaler) i MDI (metered-dose pressurized inhaler), svaki sa svojim specifičnim karakteristikama, prednostima i manama. Dosadašnje studije nisu pokazale značajnu razliku u kontroli bolesti ovisno o tipu inhalera koji se primjenjuje. Za kontrolu bolesti ključnom se pokazala pravilna inhalatorna tehnika. Edukacija bolesnika ključni je faktor u primjeni uređaja za inhalaciju, kao i u efektivnosti inhalatorne terapije. Neovisno o tome koji se inhaler odabere, edukacija od strane medicinskog osoblja bitna je u poboljšanju inhalatorne tehnike i konačno boljoj kontroli astme.Asthma is a chronic inflammatory disease of the respiratory system whose treatment is primarily based on use of the inhalation therapy. However, even with an effective inhalation therapy, many patients have problems with asthma control. Although there are various reasons for inappropriate asthma control, one of the most signifi cant reasons is poor education about inhalation techniques. Metered Dose Inhalers (MDIs) and Dry Powder Inhalers (DPIs) are the most commonly used delivery devices in asthma treatment. Each of them has specific characteristics, advantages and disadvantages. Previous studies have shown no significant difference in disease control depending on a type of the inhaler used. This study will point out how a correct inhalation technique is crucial for disease control. Adequate and patient-friendly education has to be a key factor for the correct use of inhalers, effectiveness of the inhalation therapy and finally, better asthma control

Endotelna funkcija i fenotipska obilježja bolesnika s kroničnom opstrukcijskom plućnom bolesti sklonih čestim egzacerbacijama [Endothelial function and phenotypic characteristics of patient with chronic obstructive pulmonary disease and frequent exacerbations]

The „frequent egzacerbator“ is a COPD phenotype characterised with severe clinical course and with increased risk for cardiovascular mortality. The systemic inflammation play a key role in the pathogenesis of COPD and endothelial dysfunction is a suspected link between increased cardiovascular mortality and systemic inflammation in COPD patients.So far, systematic studies of endothelial dysfunction in two phenotypically distinct groups of COPD patients has not been done. The study recruited 117 participants. COPD patients were divided into two groups according to the criteria of frequency of acute egzacerbation: 41 frequent egzacerbator and 41 infrequent egzacerbator. The control group consists of 35 healthy smokers. In all three groups were determined markers of endothelial dysfunction ( ET-1,vWF) and of systemic inflammation ( WBC, fibrinogen, CRP). We conducted pulmonary function test and 6-MWT-minute walking test, and calculated BODE indeks. Endothelial function was assessed by FMD. The results were statistically analyzed. Frequent exacerbator had more severe airway obstruction and higher degree of sistemic inflammation and endothelial dysfunction, with higher symptom score and BODE index.We believe that our research will represent a significant contribution to better understanding, early detection and adequate treatment of these groups of COPD patient

Characteristics of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Pneumonije su jedna od najtežih komplikacija KOPB-a i ujedno jedna od najčešćih infekcija u bolesnika s njime, koja znatno pridonosi pogoršanju osnovne bolesti. Upale pluća u bolesnika s KOPB-om pokazuju određenu specifičnost u odnosu prema općoj populaciji ne samo u pogledu najčešćih uzročnika, simptoma bolesti i razine upalnog odgovora već i duljine liječenja i terapijskog pristupa. Pneumonije u bolesnika s KOPB-om treba pravodobno dijagnosticirati i liječiti te razlikovati od akutnih egzacerbacija KOPB-a, a unatoč tomu što dovode do težega kliničkog tijeka i duljeg liječenja s češćim hospitalizacijama ne utječu znatno na ukupni mortalitet bolesnika s KOPB-om.Pneumonia is one of the most severe complications of COPD and also one of the most common infections in COPD patients, contributing significantly to the worsening of the underlying disease. Compared to the general population, pneumonia in COPD patients is differentiated not only by microbial etiology, clinical presentation and the level of the inflammatory response, but also by the length of treatment and the therapeutic approach. Pneumonia in COPD patients should be diagnosed and treated on time and it should be differentiated from the acute exacerbation of COPD in terms of baseline severity, microbiology, and inflammatory pattern. Despite worse clinical presentation and lengthier treatment with more frequent hospitalisations, the mortality rate of COPD patients is similar to that of non-COPD patients

Imunosupresivno liječenje nakon transplantacije pluća

Lung transplantation has become a life-saving procedure for individuals with variety of end-stage respiratory diseases. Optimal immunosuppression remains the key to long-term graft survivival. The protocols for immunosuppressive therapy following lung transplantation can be divided into three general categories: induction, maintenance, and treatment of rejection. The goal of induction therapy is to provide intense immunosuppression in the early post-transplantation period, when the risk of allograft rejection is the highest. Induction agents primarily target T lymphocytes, which are considered the effector cells in cell-mediated rejection. Current maintenance therapy typically includes a calcineurin inhibitor, nucleotide blocking agent and corticosteroid. Pulse steroids are generally the first treatment of acute cellular rejection. Therapeutic modalities for treatment of refractory cellular rejection include switch from cyclosporine to tacrolimus, use of lymphocyte depleting agents, azithromycine, and extracorporeal photopheresis. Treatment options for humoral rejections include plasmapheresis and immunoglobulines in combination with rituximab.Transplantacija pluća je postupak koji spašava život bolesnicima s krajnjim stadijem različitih plućnih bolesti. Optimalna imunosupresija predstavlja ključ dugotrajnog preživljenja presadka. Protokoli imunosupresivnog liječenja nakon transplantacije pluća mogu se podijeliti u tri glavne grupe: indukcijska terapija, terapija održavanja i terapija liječenja reakcija odbacivanja. Cilj indukcijske terapije je osigurati intenzivnu imunosupresiju u ranom posttransplantacijskom periodu, kada je rizik odbacivanja alografta najveći. Indukcijski lijekovi su primarno usmjereni na T limfocite, koji se smatraju glavnim stanicama u stanično posredovanoj reakciji odbacivanja. Trenutno se terapija održavanja tipično sastoji od inhibitora kalcineurina, antimetabolita i kortikosteroida. Pulsne doze kortikosteroida su prvi izbor liječenja akutnog staničnog odbacivanja. Načini liječenja refraktornog staničnog odbacivanja uključuju zamjenu ciklosporina takrolimusom, primjenu monoklonalnih i poliklonalnih antilimfocitnih protutijela, azitromicina i ekstrakorporalne fotofereze. Mogućnosti liječenja humoralnog odbacivanja uključuju plazmaferezu i imunoglobuline u kombinaciji s rituksimabom

Angiotensin-converting Enzyme 2 (ACE2) as a potential diagnostic and prognostic biomarker for chronic inflammatory lung diseases

Chronic inflammatory lung diseases are characterized by uncontrolled immune response in the airways as their main pathophysiological manifestation. The lack of specific diagnostic and therapeutic biomarkers for many pulmonary diseases represents a major challenge for pulmonologists. The majority of the currently approved therapeutic approaches are focused on achieving disease remission, although there is no guarantee of complete recovery. It is known that angiotensin-converting enzyme 2 (ACE2), an important counter-regulatory component of the renin–angiotensin–aldosterone system (RAAS), is expressed in the airways. It has been shown that ACE2 plays a role in systemic regulation of the cardiovascular and renal systems, lungs and liver by acting on blood pressure, electrolyte balance control mechanisms and inflammation. Its protective role in the lungs has also been presented, but the exact pathophysiological mechanism of action is still elusive. The aim of this study is to review and discuss recent findings about ACE2, including its potential role in the pathophysiology of chronic inflammatory lung diseases:, i.e., chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. Additionally, in the light of the coronavirus 2019 disease (COVID-19), we will discuss the role of ACE2 in the pathophysiology of this disease, mainly represented by different grades of pulmonary problems. We believe that these insights will open up new perspectives for the future use of ACE2 as a potential biomarker for early diagnosis and monitoring of chronic inflammatory lung diseases

Have we Made Progress in Treating COPD?

Od daleke 1965. kada je prvi puta dr. William Briscoe upotrijebio izraz kronična opstruktivna plućna bolest (KOPB) pa sve do danas, rasla su i mijenjala se saznanja o KOPB-u, a s njima i liječenje ove kronične i progresivne bolesti. Bronhodilatatori su i dalje osnova liječenja, a primjena kombinirane terapije ili najnovije trojne terapije namijenjena je bolesnicima s više simptoma i čestim egzacerbacijama. Daleko veće promjene je doživio sam terapijski pristup. U prošlosti se odluka o liječenju temeljila na stupnju opstrukcije za razliku od današnjeg pristupa, kada težimo personalizaciji u liječenju KOPB-a. Na raspolaganju nam stoje brojni novi lijekovi u različitim inhalatornim uređajima, čime možemo osigurati bolesniku s KOPB-om najbolji terapijski odabir u inhaleru koji najviše odgovara bolesnikovim potrebama. Osim farmakološkog napretka u liječenju KOPB-a, treba istaknuti i razvoj nefarmakoloških metoda liječenja, prije svega plućne rehabilitacije, kao sastavne i ravnopravne komponente u zbrinjavanju bolesnika s KOPB-om. Međutim, današnje liječenje usmjereno je ponajprije zbrinjavanju bolesnika sa značajnim simptomima bolesti. Nedostaju nam lijekovi koji bi mijenjali sam tijek bolesti, odnosno zaustavili daljnju progresiju bolesti. Ne postoje definirane opcije za rani KOPB. U tijeku su brojna istraživanja različitih lijekova za koje se očekuje da budu učinkovita. Međutim za sada niti jedna od ispitivanih opcija nije dovela do značajnijih pomaka. Koliko god nam se činilo da znamo sve o KOPB-u, još uvijek ne znamo dovoljno da bismo ga izliječili.The knowledge about COPD has grown and changed since 1965 when Dr. W. Briscoe first used the term chronic obstructive pulmonary disease (COPD). At the same time, knowledge about the treatment has grown as well. Bronchodilators are still the first-line therapy for COPD, while combination therapies, especially triple combination therapy, are reserved for more symptomatic patients and patients with frequent exacerbations. The therapeutic approach has undergone far greater changes. In the past, treatment recommendation was based primarily on the level of airflow limitation. The assessment system was refined, and today we have the A, B, C, and D groups that define the pharmacological treatment based on symptoms and exacerbation history only. Numerous new drugs are available for patients in a variety of inhaler devices, allowing us to provide COPD patients with the best therapeutic choice in the inhaler that is best for them. In addition to pharmacological advances in COPD treatment, it is necessary to emphasize the development of non-pharmacological methods, primarily pulmonary rehabilitation. However, the direction of treatment is aimed primarily at caring for patients with significant symptoms. We lack drugs that would change the course of COPD and stop further progression of the disease. In addition, there are no defined options for early COPD. Numerous studies of various drugs are expected to be effective, but none of the options examined led to significant progress so far. As much as we think we know everything about COPD, we still do not know enough to cure it

Nasal polyposis in cystic fibrosis: experience from CF Center, UHC Zagreb

Cystic fibrosis (CF) is a lethal autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator gene (CFTR). CFTR mutations affect epithelial cells in the lungs, sinuses, pancreas, liver, kidneys, intestine and sweat glands, causing abnormally viscous mucus production, thickening of digestive fluids and salty sweat. The consequences for the respiratory system are mucus buildup, decreased mucociliary clearance and tissue inflammation. A change in microbioma follows, with S. aureus and P. aeruginosa being prevalent in most patients, as they have the capacity of biofilm formation causing chronic colonization. This represents the basis for recurrent infection. At the same time, pancreatic insufficiency leads to malabsorption of fat-soluble vitamins, i.g. vitamin D3, a powerful immunomodulator implicated in both pulmonary and sinus pathophysiology. CF is marked by a high incidence of nasal polyposis, even in the pediatric population and ENT follow-up is mandatory. CF nasal polyposis is a distinctive form of nasal polyposis and its treatment and follow up present many challenges. CF affects one out of every 3000 newborns. The total number of patients with CF in Croatia is 175, and the majority of them now refer to our CF Center of Zagreb University Center where they are approached by a multidisciplinary team: both pediatric and adult pulmologists, gastroenterologists, endocrinologists, rhinologists, microbiologists and nutritionists. We aimed to review our experience with CF patients from a rhinologist point of view and present the prevalence and specifics of nasal polyposis in cystic fibrosis patients from our CF Center