Background: In chronic obstructive pulmonary disease (COPD), understanding the problem of poor patient participation in evidence-based self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as SM support programmes) is critical. This thesis aimed to improve understanding of poor patient participation and retention in these programmes; how participation might be improved; and how might patients be better supported with their SM. Methods: Using the Medical Research Council guidance on complex interventions this thesis (1) quantified the 'actual' patient participation and completion rates; (2) explained, using theory, the factors that influenced participation in studies of SM support including the programmes among chronic disease and COPD patients; and (3) explored patient and expert stakeholders' perspectives on the reasons for non-participation in SM support programmes, how participation might be improved, how might patients be supported with their SM. Results: (1) Among 56 studies, high study participation rates and completion rates were seen however, the incomplete reporting of participant flow confused the problem of participation. (2) Among 31 studies, participation among patients with chronic disease including COPD was shown to be influenced by their 'attitude' and 'perceived social influence/subjective norms'; 'illness' and 'intervention perceptions'. (3) From 38 interviewees, besides patients' beliefs, non-participation was also influenced by resignation and denial of the illness; health systems; and programme organisational factors. Professionals building relationships and supporting patients with their SM alongside programme organisational improvements might encourage patient participation in SM and the programmes. Conclusions Patient participation is a complex behaviour, besides socio-behavioural factors, participation behaviour can by influenced by a mix of several health system and programme organisational factors. Changing the behaviour of health professionals and indeed the wider health system, towards normalising a patient partnership approach, with implementation of SM support in routine care might help more patients to consider participation in their care and improve patient participation in COPD SM support programmes.

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Chronic lung diseases are often complicated with pulmonary hypertension (PH). This can lead to disability and poor prognosis. Oxidative stress has been implicated in the development of PH and right ventricular hypertrophy (RVH).A possible new way to treat lung disease related pulmonary hypertension is allopurinol (a xanthine oxidase inhibitor) which decreases both uric acid and oxidative stress. We hypothesised that allopurinol could regress RVH in patients with pulmonary hypertension associated with chronic lung disease (PH-CLD).In a double-blind, randomised controlled clinical trial, 72 patients with PH-CLD (93% diagnosed with chronic obstructive pulmonary disease and 17% with interstitial lung disease) were randomised to receive either allopurinol 300 mg twice daily or placebo for twelve months. The primary outcome was the mean change in right ventricular mass (RVM) as assessed by cardiac magnetic resonance imaging (CMRI) at twelve months. The secondary outcomes were the change in other cardiac parameters measured by CMRI, St George's Respiratory Questionnaire, Short Form 36, spirometry and six-minute walk test (6MWT).The mean age was 71 years, the mean FEV1 was 60% with mean resting SaO2 of 96%. After 12 months, there was no significant change in RVM. There were also no significant changes in other cardiac parameters measured on CMRI, quality of life questionnaires, spirometry and 6MWT. Post-hoc subgroup analysis showed that allopurinol reduced RVM (allopurinol -6.16 g vs placebo 0.75 g, p = 0.02) in COPD patients with more severe airflow limitation. Patients with higher NT-proBNP (> 489 pg/ml) had a greater improvement in left ventricular ejection fraction with allopurinol 5.12 vs placebo -1.62, p = 0.02.In summary, allopurinol had no overall impact but reduced RV mass in COPD patients with more severe airflow limitation. Further studies are warranted to assess the longer term impact of allopurinol in more severe COPD.

Significant cardiovascular morbidity and mortality exists in chronic obstructive pulmonary disease independent of traditional risk factors. A number of different hypotheses exist to explain this association including the contribution arterial stiffness and lung hyperinflation. Non-invasive cardiovascular imaging and assessment are ideal methods through which this relationship can be further studied although a number of the techniques have yet to be validated in COPD. In this thesis we aimed to achieve a number of goals. First, we aimed to assess the reproducibility and level of agreement between different measures of arterial stiffness in stable hyperinflated COPD. Second, we hoped to establish the utility of 3 different measurement techniques for measuring intrinsic cardiac function in stable hyperinflated COPD. Third, in a case-control study we compared surrogates of cardiovascular risk in hyperinflated COPD patients and a group matched for cardiovascular risk with normal lung function. Finally, we sought to understand the impact of pharmacologically reducing lung hyperinflation on cardiovascular structure, function and arterial stiffness. We have firstly demonstrated that non-invasive measures of arterial stiffness are reproducible in stable hyperinflated COPD. Secondly, we have established the level of agreement and reproducibility of three different CMR techniques for measuring intrinsic myocardial function which will provide important information for the powering of future CMR studies in COPD. Thirdly, we have shown that surrogates for cardiovascular outcomes are adversely affected in COPD compared to a group matched for global cardiovascular risk, suggesting that current scoring systems may be suboptimal in risk prediction in COPD. Finally, we have demonstrated that pharmacological lung deflation has consistent and physiologically plausible beneficial effects on cardiac structure, function and the pulmonary vasculature. Whether intrinsic myocardial function can be modulated through prolonged periods of lung deflation is as yet unverified and should be the focus of future clinical trials.

Made available in DSpace on 2014-06-11T19:22:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-25Bitstream added on 2014-06-13T19:48:22Z : No. of bitstreams: 1 servio_tc_me_botfm.pdf: 1055866 bytes, checksum: d86e7a487aac3e078c759f6ceaf80ca8 (MD5) / Universidade Estadual Paulista (UNESP) / A Doença de refluxo gastroesofágico é uma afecção muito comum. Atualmente, o tratamento cirúrgico videolaparoscópico tem sido amplamente empregado. Porém, apesar de ser uma técnica minimamente invasiva, pode acarretar uma série de alterações pulmonares importantes. Analisar as alterações funcionais respiratórias em indivíduos submetidos à válvula anti-refluxo videolaparoscópica. Foram avaliados, pela equipe do Hospital Estadual Bauru, no período de março de 2009 até maio de 2010, todos os pacientes com indicação cirúrgica. No período pré-operatório todos foram submetidos à anamnese, espirometria, medida do índice diafragmático, ventilometria, manovacuometria, pico de fluxo expiratório, teste de caminhada de 6 minutos e teste de escada. Todos os testes foram repetidos no primeiro, segundo, quinto e trigésimo pós-operatórios. Somente o teste de escada não foi repetido no primeiro pós-operatório. Foi avaliada em cada pós-operatório a escala analógica de dor, e a escala de Borg foi aplicada após os testes dinâmicos. Foram avaliados 32 pacientes, sendo 59% mulheres. A média da idade e do IMC foi de, respectivamente, 44,4±10,9 anos e 28,4±4,8 kg/m2. A amostra foi formada por 75% de não tabagistas, 6% de tabagistas e 19% de ex-tabagistas. Não houve qualquer caso de complicação pós-operatória. O VEF1, CVF, VVM e o PFE apresentaram queda significativa no PO1 e PO2, voltado aos valores pré no PO5. A PImáx e PEmáx apresentaram queda significativa no PO1, mantendo-se no PO2 ainda baixas, mas sem significância estatística com o pré, sendo que no PO5 seus valores já eram superiores aos do PO1 e semelhantes ao pré. O VE teve incremento estatisticamente significativo no PO2, ficando nos outros momentos em valores intermediários entre os valores PRÉ e PO2, enquanto a f teve acréscimo estatisticamente significante no PO1e nos outros momentos... / Gastroesophageal reflux disease is a very common condition. Currently, the laparoscopic surgical treatment has been widely used. However, despite being a minimally invasive technique, it may lead to a series of major pulmonary changes. Evaluate changes in respiratory function in patients who underwent laparoscopic anti-reflux valve. All patients with surgical indications were evaluated by the team of Bauru State Hospital, from March 2009 until May 2010. In the preoperative period all patients underwent history taking, spirometry, measurement of diaphragmatic index, respirometry, manometer, expiratory peak flow, 6-minute walking test and stairclimbing. All the tests were repeated in the first, second, fifth and thirtieth postoperative days. Only the stair climbing test was not repeated in the first postoperative day. It was assessed at each postoperative day the pain analog scale and the Borg scale was applied after the dynamic tests. We evaluated 32 patients, 59% women. The mean age and BMI was respectively 44.4 ± 10.9 years and 28.4 ± 4.8 kg/m2. The sample comprised 75% of nonsmokers, 6% of smokers and 19% of former smokers. There was no case of postoperative complication. FEV1, FVC, MVV and EPF showed significant decrease in PO2 and PO1, and it returned to baseline levels in PO5. The MIP and MEP showed a significant drop in the PO1, PO2 remaining at still low, but without statistical significance with the PRE, while in PO5 their values were already higher than PO1, and similar to the PRE. The MV had statistically significant increase in PO2, presenting at other times intermediate values between PRE and PO2, whereas the f had statistically significant increase in PO1 and presenting at other moments intermediate values to PRE and PO2. The TV and ID did not differ significantly at any time. The distance in 6MWT showed a significant drop in the PO1, and PO2. In PO5 there was no statistical... (Complete abstract click electronic access below)

Background: Lung clearance index (LCI), obtained by multiple breath washout testing (MBW), is a sensitive measure of lung disease in infants. It has been identified as a particularly suitable endpoint for clinical trials in cystic fibrosis (CF), but has potential applications in many other conditions. However, MBW in infants presents a number of technical challenges. Conventional MBW is based on simultaneous measurement of flow and gas. These two signals are then aligned and combined to derive expired gas volumes and measures of ventilation inhomogeneity: this process becomes increasingly vulnerable to errors in gas signal alignment at rapid respiratory rates. At present, no existing system for infant MBW meets all the criteria set out in international guidelines, and there is no simple method of assessing lung function outside research laboratories in this population. This thesis describes an alternative method of performing MBW in infants. In this method, expired gas is collected and analysed to derive functional residual capacity (FRC) and LCI. There is no need to simultaneously measure flow, and therefore no need for the complicated step of integrating flow and gas signals. Dead space is also significantly reduced by removing the flowmeter. Methods: In the first phase of testing, an existing lung model was modified to generate realistic infant breathing parameters with high accuracy. The prototype system was modified to improve accuracy and subsequently tested at FRC of 100-250mls with respiratory rates of 20-60min-1. In the second phase, testing proceeded to an in vivo pilot study of the novel method in children with cystic fibrosis and healthy controls. Practical applicability of the system was determined by the number of successful duplicate tests, and within-subject repeatability. Comparison was made with LCI measurements obtained using a respiratory mass spectrometer, currently considered the gold standard for infant LCI. Results: In a total of 103 tests performed in the lung model, overall mean error (standard deviation) of FRC measurement was -1.0(3.3)%, with 90% of tests falling within +/-5%. 13 patients were excluded from the clinical study due to being unsedated or inadequately sedated and therefore failing to tolerate the test. A total of 25 patients (7 children with CF, 18 healthy control children) were deemed to be adequately sedated at the start of the test, of these 20 patients (7 with CF) successfully underwent duplicate testing (80% success rate). Mean FRC for healthy controls was 19.5ml/kg, and mean LCI 6.45. For children with CF, mean FRC was 21.8ml/kg and mean LCI 6.98. Mean within-subject coefficient of variation for FRC was 7.18% and for LCI 5.94%. Of 4 infants assessed with both the novel method and the respiratory mass spectrometer, there was good correlation in FRC measurement (mean difference -8.1%). Comparison of LCI with the mass spectrometer was affected by technical difficulties with the test; in those patients who underwent technically adequate tests with both methods, mean difference in LCI between the two methods was 1.65%. Discussion: FRC measurement using the novel method has superior accuracy in vitro than previously described systems. Data from the pilot study suggest that this is a feasible and reproducible method of performing LCI in infants and young children, as long as they are adequately sedated. Results in both children with CF and controls fall within the expected range, and well within accuracy limits set by international guidelines. However, the system and testing protocol could be further improved to reduce the number of technically inadequate tests having to be excluded. This could provide a more accessible alternative to previously described systems for infant MBW.

Background: Chronic obstructive pulmonary disease (COPD) is an important common chronic lung condition that is a leading cause of morbidity and mortality worldwide, resulting in a substantial and increasing economic and social burden to health care systems. Physical activity (PA) is the strongest predictor of mortality in this population, playing an important role determining the quality of life in COPD, with better outcomes being reported by those who have higher levels of PA. Therefore, improving PA levels has been considered a key component in the management of patients with COPD. Likewise, it is important to understand the mechanisms that lead to inactivity, as it is to develop accurate methods of measuring PA in this population. Aims of the thesis: 1) To identify and to summarize the interventions able to increase PA levels in patients with COPD; 2) To understand the longitudinal interaction between muscle mass and function and PA levels in COPD; 3) To study the acceptability and the suitability of a new activity monitor (TracMor D - Philips, the Netherlands) for home coaching in daily routine of patients with COPD; and 4) To investigate whether a PA enhancing programme with set targets and feedback would constitute a successful intervention to increase PA levels in patients with COPD attending pulmonary rehabilitation (PR). Methods: To achieve the first aim of the thesis I performed a systematic review summarizing interventional studies that assessed PA as an outcome in patients with COPD. For the second aim, I analysed some multicentric longitudinal data (one year follow-up) on PA and muscle mass/function in COPD. The third aim was achieved with a pilot study I conducted in Edinburgh, where patients with COPD wore three TracMor D in different body places simultaneously with the criterion method (Actigraph GT3x activity monitor) for a week. To accomplish the fourth and main aim of my PhD, I conducted a randomised controlled trial (RCT) where patients with COPD undergoing PR were randomised to either receive PR only or PR plus a PA coaching programme using the TracMor D activity monitor for 12 weeks. Main Results: Study 1: Sixty studies were considered for data extraction in the systematic review. Seven types of intervention with the potential to increase PA levels in patients with COPD were identified. PR programmes with more than 12 weeks of duration and PA coaching programmes with feedback of an activity monitor are promising interventions to increase activity levels in patients with COPD. Overall, the quality of evidence across interventional studies was graded as very low. Study 2: The longitudinal study showed that there were weak correlations between PA levels and muscle strength at baseline (0.19 ≤ r ≤ 0.33 p < 0.001 for all). No correlations were found between changes in PA and muscle strength (-509 [-1295-362] vs -0.4 [-3.5-2.6] - 12 months minus baseline - respectively) and future muscle mass (p > 0.05). Baseline PA levels are related to future muscle strength (0.30 ≤ r ≤ 0.41, p < .0001) but not with muscle mass. Study 3: This study showed that TracMor D had strong correlations with Actigraph GT3x in terms of Kcal consumption in all three positions (necklace, pocket and hip) (0.84 ≥ r < 0.86, p < 0.001 for all). TracMor D was considered comfortable and easy to use at home, receiving a mean usability score of 98 out of 100 maximum points. Study 4: My RCT showed that the proposed PA intervention was effective in changing steps/day (1251 ± 2408 vs control -410 ± 1118, p=0.01), time spent in light activities (21 ± 60 vs -37 ± 55, p=0.004), exercise capacity (99 ± 139 vs 3 ± 83 meters; 85 ± 114 vs 2 ± 62 seconds, p < 0.03 for both) and muscle strength (15 ± 20 vs -5 ± 18, p=0.01) among others when compared to the control group. Conclusions: Strategies focussing specifically on increasing PA and longer PR programmes may have greater impacts on PA levels in COPD. Well-designed clinical trials with objective assessment of PA in patients with COPD are needed. PA levels are not related to one-year changes in muscle mass and muscle strength in patients with COPD. However, higher PA levels at baseline are related to having higher muscle strength at one-year. TracMor D strongly correlated with the criterion method and was highly accepted by patients with COPD in their daily routine, being considered comfortable and easy to use at home. The combination of PR with a physical activity enhancing programme using a PA monitor to set targets and give feedback on activity levels significantly improves PA, exercise capacity, muscle strength, quality of life, and anxiety and depression levels in patients with COPD.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / Chronic obstructive pulmonary disease is a common, avoidable and treatable disease characterized by persistent obstruction of the airways and lungs. This disease is usually progressive and associated with a chronic inflammatory response set off by noxious particles or gases. Patients with chronic obstructive pulmonary disease, represents a great impact on the increase of clinical care, as well as the economic health spending to provide better quality of life. This study characterizes the pharmacoepidemiological profile, adherence to drug therapy, pharmacotherapy complexity and performance of using inhalation devices in outpatientâs subjects of a referral hospital for treatment of pulmonary diseases. This is a descriptive, exploratory and transversal study. 83 individuals were interviewed, with a predominance of males, a mean age of 68.22 years, and low schooling. The average number of medications per patient was 5.58, characterizing the polypharmacy, and 81.9% had some type of comorbidity. The founded prevalence was mean adherence rate (45.8%). The most frequent response among the questions asked to measure adherence was related to forgettings (38.6%). The complexity therapy had a mean value of 15.9 points, a high score that reveals the difficulties in following the treatment. After evaluation of inhalation devices was found that as the use of dry powder inhaler Aerolizer, the technique was considered good in 62.5% of patients, the use of Respimat  inhaler was "good" in 70.96% of cases and the use of metered-dose aerosol showed to be regular in 64.7%. The evaluation of the use of the devices found flaws in several steps considered essential for their proper management. From these data, are needed strategies that aimed at enhancing actions to improve adherence to therapy and ongoing evaluation of inhalation devices, minimizing complications for the patient. / A DoenÃa pulmonar obstrutiva crÃnica, à uma doenÃa comum, evitÃvel e tratÃvel, caracterizada por obstruÃÃo persistente das vias aÃreas e dos pulmÃes, geralmente progressiva e associada a uma resposta inflamatÃria crÃnica desencadeada por partÃculas ou gases nocivos. Os pacientes portadores de DoenÃa pulmonar obstrutiva crÃnica representam um grande impacto no aumento dos atendimentos clÃnicos, assim como nos gastos econÃmicos com a saÃde para proporcionar melhor qualidade de vida. Este trabalho caracteriza o perfil farmacoepidemiolÃgico, a adesÃo à terapia medicamentosa, complexidade da farmacoterapia e o desempenho do uso de dispositivos inalatÃrios em indivÃduos atendidos em um ambulatÃrio de um hospital de referÃncia em tratamento de doenÃas pulmonares. Trata-se de um estudo descritivo, exploratÃrio e transversal. Foram entrevistados 83 indivÃduos, com predominÃncia do sexo masculino, idade mÃdia de 68,22 anos e baixa escolaridade. A mÃdia do nÃmero de medicamentos por paciente foi de 5,58, caracterizando a polifarmÃcia, e 81,9% tinham algum tipo de comorbidade. A prevalÃncia encontrada foi de mÃdia adesÃo (45,8%). A resposta mais frequente entre as perguntas realizadas para mensurar a adesÃo foi a referente aos esquecimentos dos pacientes em tomarem seus medicamentos diariamente (38,6%). A complexidade terapÃutica teve valor mÃdio de 15,9 pontos, um escore elevado que revela as dificuldades existentes no seguimento do tratamento. ApÃs avaliaÃÃo dos dispositivos inalatÃrios constatou-se que quanto ao uso de inaladores de pà seco Aerolizer a tÃcnica foi considerada boa em 62,5% dos pacientes, o uso de inalador Respimat foi âbomâ em 70,96% dos casos e o uso de aerossol dosimetrado mostrou-se regular em 64,7%. A avaliaÃÃo do uso dos dispositivos encontrou falhas em vÃrias etapas consideradas essenciais para o seu manejo adequado. A partir destes dados, se fazem necessÃrias estratÃgias que visem potencializar aÃÃes para melhorar a adesÃo à terapia e uma avaliaÃÃo contÃnua do uso dos dispositivos inalatÃrios, minimizando complicaÃÃes para o paciente.

O presente trabalho estuda alguns aspectos epidemiológicos da tuberculose pulmonar na Casa de Detenção de São Paulo, Brasil, durante o período de 1976 a 1980. São analisados dados relativos à prevalência e incidência da infecção tuberculosa, busca de casos pelo método bacteriológico e taxa de transmissibilidade da infecção. Os resultados mostram elevadas taxas de prevalência e incidência de infecção e de casos de tuberculose naquele Estabelecimento Penal, caracterizando população exposta a um alto risco de infecção e de adoecimento por tuberculose. / This paper presents some epidemiological aspects of pulmonary tuberculosis in a state prision of S.Paulo, Brazi1, from 1976 to 1980. Data concerning both the prevalence and incidence of tuberculosis infection, case finding by the bacteriological method and infectivity rate are analysed. Results show high rates of prevalence and incidence of infection as well as of active cases in that institution, characterizing this population as one being exposed to a high risk of infection and of developing tuberculosis.

Pulmonary fibrosis (PF) is a serious lung disease, as its life expectancy is only 3-5 years upon occurrence and more than 50 % of the cases are idiopathic, i.e., unknown cause. Two drugs, pirfenidone (PIR) and nintedanib, have recently been approved; however, their efficacies are moderate without evidence of prolonged survival. While this is primarily due to our insufficient knowledge about key PF pathogenesis, inductions of oxidative stress and transforming growth factor-b1 (TGF-b1) have been suggested in PF lungs. Hence, anti-oxidative melatonin (MEL) and curcumin (CUR) have been studied yet their efficacies remain moderate without clear understanding about the mechanisms of action. Accordingly, this project hypothesized that a novel hybrid molecule of MEL and CUR, AM24, was a more potent inhibitor against oxidative stress and TGF-b1 induced PF pathobiologic events than MEL or CUR, so that its pulmonary delivery enabled therapeutic intervention in an animal model of PF. Free radical scavenging activity and various in vitro lung cell-based anti-fibrotic activities of AM24 were determined and compared with those of MEL and CUR as well as their admixture (MEL+CUR) and PIR. Pulmonary administration of AM24 was then examined for therapeutic intervention in a rat model of bleomycin (BLM)-induced experimental PF. AM24 was equipotent to MEL, but less potent than CUR in the hydrogen peroxide-induced free radical (ABTS) scavenging assay, ranked with the half-maximal inhibitory concentration (IC50) of 25.7, 32.0 and 11.4 uM, respectively. However, in the in vitro human lung fibroblast systems, AM24 was shown to be more potent than MEL or CUR and notably than MEL+CUR or PIR in the TGF-b1 induced 1) collagen synthesis by the picrosirius red assay, 2) proliferation by the MTT assay; and 3) differentiation to myofibroblast by western blot analysis of a myofibroblast marker, a-smooth muscle actin (a-SMA). In detail, at 10 uM, AM24 inhibited TGF-b1 induced 1) collagen synthesis by 90 %; 2) proliferation by ~72 %; and 3) differentiation to myofibroblast completely, while MEL, CUR, MEL+CUR and PIR resulted in 30-55 % or insignificant inhibition. In addition, in the in vitro human lung alveolar epithelial cell system, AM24 at 10 uM almost completely inhibited TGF-b1 induced epithelial-mesenchymal transition (EMT), as measured with western blot expressions of an epithelial marker, E-cadherin, and a mesenchymal marker, vimentin. Again, MEL, CUR, MEL+CUR and PIR exerted much less inhibitory activities. Hence, all these results consistently suggested that AM24 was a unique hybrid molecule of MEL and CUR and possessed highly potent anti-fibrotic activities in addition to the free radical scavenging activity. AM24 was then examined for therapeutic intervention in an in vivo rat model of BLM-induced PF. BLM was orotracheally spray-dosed to the lungs at 0.6 mg/kg on day 1 to develop experimental PF in 14 days. Lung administrations of AM24 at 0.1 mg/kg commenced at 6 hours of BLM induction on day 1 and continued thrice weekly over two weeks. Functional treadmill exercise endurance was measured on day 12 and 15; and lungs were harvested upon sacrifice on day 16. Overall, AM24 showed significant intervention activities as follows: 1) exercise endurance was reduced only ~20%, much lower than 78% of the untreated PF rats; 2) reduced fibrotic tissue area and alveolar structural destruction were seen by histological examinations; and 3) lung’s induced collagen deposition was inhibited by ~78 %. However, unlike the literature, the lung’s TGF-b1, PCNA (a cell proliferation marker), and a-SMA (a differentiation marker), were not largely induced in the BLM-induced PF model, so that the intervention activities of AM24 to these markers were not clearly shown. In contrast, induced EMT was seen in the BLM-induced model, represented by increased mesenchymal marker, vimentin, and by decreased epithelial marker, E-cadherin; and AM24 appeared to counter this induced EMT. Accordingly, while the BLM-induced PF model may need further optimizations for clearer pathogenic changes, AM24 exerted certain degree of in vivo efficacies with a lung dose of 0.1 mg/kg, which was much lower than the effective doses of MEL, CUR, PIR and nintedanib seen in the literature with BLM induced PF model. In conclusion, this thesis study has provided an early proof-of-concept for AM24, a novel MEL-CUR hybrid molecule, being potently anti-oxidative and anti-fibrotic in the in vitro lung cell-based assessments. As a result, AM24 enabled therapeutic intervention just with a lung dose of 0.1 mg/kg in the BLM-induced rat model of experimental PF.