Rice Bran Oil Improves Emphysema in Cigarette Smoke Extract-Induced Mice through Anti-Inflammatory and Antioxidative Effects.

Lung inflammation and alveolar enlargement are the major pathological conditions of chronic obstructive pulmonary disease (COPD) patients. Rice bran oil (RBO), a natural anti-inflammatory and antioxidative agent, has been used for therapeutic purposes in several inflammatory diseases. This study aimed to investigate the anti-inflammatory and antioxidative effect of RBO on a cigarette smoke extract (CSE)-induced emphysema model in mice. The results indicated that CSE significantly induced airspace enlargement in mouse lung. Increased inflammatory cells, macrophage, and TNF-alpha levels in bronchoalveolar lavage fluid (BALF) were noticed in CSE-treated mice. RBO (low and high dose)-supplemented mice showed decreased total BALF inflammatory cell, macrophage, and neutrophil numbers and TNF-alpha levels (p < 0.05). Additionally, the administration of RBO decreased the mean linear alveolar intercept (MLI) in the CSE-treated group. Additionally, RBO treatment significantly increased the total antioxidant capacity in both mouse BALF and serum. However, RBO did not have an effect on the malondialdehyde (MDA) level. These findings suggested that RBO treatment ameliorates lung inflammation in a CSE-induced emphysema mice model through anti-inflammatory and antioxidant pathways. Therefore, the supplementation of RBO could be a new potential therapeutic to relieve the severity of COPD.

Emphysematous pyelonephritis with progression to necrotising fasciitis of the posterior cervical region and the retropharyngeal space.

A man in his 50s with diabetes presented with backache, left flank pain and fever. On evaluation, he was found to have emphysematous pyelonephritis of the left kidney with a paranephric abscess extending into the posterior abdominal wall and superiorly up to the posterior chest wall and inferiorly extending up to the posterior superior iliac spine. The management involved the initiation of broad-spectrum antibiotics and percutaneous drainage of the abscess. However, as he continued to worsen symptoms-wise, he underwent computed-enhanced CT of the abdomen and thorax. The imaging revealed the presence of a purulent collection in the left lumbar region with an extension along the posterior cervical region and the retropharyngeal space. He underwent a fasciotomy of the lumbar region. The occurrence of emphysematous pyelonephritis along with necrotising fasciitis is uncommon and requires early aggressive management with broad-spectrum antibiotics and adequate drainage. This emphasises the need for early reimaging if the patient does not settle with antibiotics or percutaneous drainage.

Terpenoids as Human Neutrophil Elastase (HNE) Inhibitors: A Comprehensive Review of Natural Anti-inflammatory Isoprenoids.

Human neutrophil elastase (HNE) is an enzyme that plays a key role in the body's inflammatory response. It has been linked to several diseases such as chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. As potential treatments for these diseases, HNE inhibitors are of great interest. Metabolites derived from plants, particularly terpenoids such as ß-caryophyllene found in black pepper and other plants, and geraniol present in several essential oils, are recognized as significant sources of inhibitors for HNE. Because of their ability to inhibit HNE, terpenoids are considered promising candidates for developing novel therapies to treat inflammatory conditions such as COPD and emphysema. Furthermore, nature can serve as an excellent designer, and it may offer a safer drug candidate for inhibiting HNE production and activity in the future. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were searched to get relevant and up-to-date literature on terpenoids as human neutrophil elastase inhibitors. This review focuses on the isolation, chemical diversity, and inhibition of human neutrophil elastase (HNE) of various terpenoids reported from natural sources up to 2022. A total of 251 compounds from various terpenoids classes have been reported. Further, it also provides a summary of HNE inhibitors and includes a thorough discussion on the structure-activity relationship.

Evaluating Novel Protein Phosphatase 2A Activators as Therapeutics for Emphysema.

The activity of PP2A (protein phosphatase 2A), a serine-threonine phosphatase, is reduced by chronic cigarette smoke (SM) exposure and α-1 antitrypsin (AAT) deficiency, and chemical activation of PP2A reduces the loss of lung function in SM-exposed mice. However, the previously studied PP2A-activator tricyclic sulfonamide compound DBK-1154 has low stability to oxidative metabolism, resulting in fast clearance and low systemic exposure. Here we compare the utility of a new more stable PP2A activator, ATUX-792, versus DBK-1154 for the treatment of SM-induced emphysema. ATUX-792 was also tested in human bronchial epithelial cells and a mouse model of AAT deficiency, Serpina1a-e-knockout mice. Human bronchial epithelial cells were treated with ATUX-792 or DBK-1154, and cell viability, PP2A activity, and MAP (mitogen-activated protein) kinase phosphorylation status were examined. Wild-type mice received vehicle, DBK-1154, or ATUX-792 orally in the last 2 months of 4 months of SM exposure, and 8-month-old Serpina1a-e-knockout mice received ATUX-792 daily for 4 months. Forced oscillation and expiratory measurements and histology analysis were performed. Treatment with ATUX-792 or DBK-1154 resulted in PP2A activation, reduced MAP kinase phosphorylation, immune cell infiltration, reduced airspace enlargements, and preserved lung function. Using protein arrays and multiplex assays, PP2A activation was observed to reduce AAT-deficient and SM-induced release of CXCL5, CCL17, and CXCL16 into the airways, which coincided with reduced neutrophil lung infiltration. Our study indicates that suppression of the PP2A activity in two models of emphysema could be restored by next-generation PP2A activators to impact lung function.

GlassiaMC: Déficit congénital en alpha1-antitrypsine / Glassia TM: congenital Alpha1-Antitrypsin Deficiency

MANDAT: À la demande du fabricant Takeda Canada Inc., l'Institut national d'excellence en santé et en services sociaux (INESSS) a procédé à l'évaluation du produit du système du sang GlassiaMC, un inhibiteur de l'alpha1-protéinase humain. Au Canada, GlassiaMC est indiqué pour le traitement d'augmentation et d'entretien de longue durée chez les adultes présentant un emphysème cliniquement manifeste attribuable à un déficit héréditaire sévère en inhibiteur de l'alpha1-protéinase (AAT), aussi appelé déficit en alpha1- antitrypsine (AAT). L'indication demandée à l'INESSS est la même. L'INESSS a réalisé les évaluations des produits ProlastinMC-C Liquid, ZemairaMC et GlassiaMC, tous des alpha1-antitrypsine plasmatiques humains, en simultané. Les avis pour ces 3 produits sont publiés au même moment. DÉMARCHE: d'évaluation Une revue des données issues de la littérature et de celles fournies par le fabricant a été réalisée afin de documenter l'efficacité, l'innocuité et l'efficience de GlassiaMC. Des données contextuelles et expérientielles issues de la consultation sont également présentées. Des analyses d'efficience et d'impact budgétaire ont été élaborées par l'INESSS. DIMENSION: populationnelle Le déficit en inhibiteur de l'alpha1-protéinase, ou déficit en alpha1-antitrypsine (DAAT), est une condition génétique rare à présentation variable qui peut entraîner des symptômes pulmonaires (emphysème, bronchite chronique et bronchectasie) et hépatiques sévères et dont la progression est souvent lente. En raison des manifestations cliniques hétérogènes et souvent tardives et de la découverte de nouveaux variants pathogéniques associés à la maladie, le DAAT est une condition sous-diagnostiquée. Les traitements usuels visent l'atténuation des symptômes respiratoires et incluent les médicaments inhalés, la réhabilitation pulmonaire et, pour certains patients, la thérapie d'augmentation qui consiste en l'administration intraveineuse hebdomadaire d'alpha1-antitrypsine (AAT) dérivé du plasma. La thérapie d'augmentation a comme objectif de ralentir la progression de l'emphysème chez les individus atteints d'un DAAT. Présentement, seul le produit ProlastinMC-C est disponible au Québec et son remboursement public n'est possible que par la mesure du patient d'exception. Des traitements qui interrompent ou ralentissent la progression de l'emphysème et la détérioration des fonctions pulmonaires et hépatiques répondraient aux besoins de santé actuels, surtout s'ils permettaient d'améliorer la qualité de vie des individus atteints et de leurs proches. Une facilitation du processus d'accès à la thérapie d'augmentation est également souhaitable. EFFICACITÉ: Chez les individus atteints de DAAT, le produit d'AAT plasmatique humain GlassiaMC est considéré comme bioéquivalent au ProlastinMC puisqu'il affiche un profil pharmacocinétique comparable à ce dernier. Aucune donnée sur la capacité de GlassiaMC à ralentir la progression de l'emphysème chez les individus atteints d'un DAAT n'a été soumise par le fabricant ou répertoriée dans la littérature. Innocuité. Le profil d'innocuité de GlassiaMC est jugé acceptable et comparable à celui du ProlastinMC. Dimension organisationnelle: La couverture des AAT plasmatiques humains est présentement réalisée par la RAMQ via la mesure du patient d'exception et les régimes d'assurance privés. Dorénavant, les AAT plasmatiques devront être inscrits à la Liste des produits du système du sang du Québec et remporter un appel d'offres d'Héma-Québec pour pouvoir être distribués. Lors de ce changement de gestion, il serait prudent d'éviter les interruptions de traitement et minimiser les conséquences qui pourraient s'y lier. DIMENSION ÉCONOMIQUE: Analyse d'efficience: Au prix soumis, GlassiaMC permettrait des économies de XX $ par semaine comparativement à Prolastin-CMC, dont l'efficience n'a pas été évaluée avant cette présente évaluation. Analyse d'impact budgétaire: Advenant l'ajout de GlassiaMC à la Liste des produits du système du sang du Québec, une augmentation du nombre de patients peut être attendue en raison des patients utilisant actuellement ProlastinMC-C à travers le régime privé d'assurance médicaments qui poursuivraient leur traitement par inhibiteur d'AAT à travers le régime public. Cette hausse de personnes couvertes par le système public (XX %) se traduirait par des coûts supplémentaires estimés à plus de 8 M$ sur 3 ans. Dimension socioculturelle Le Québec s'est doté en 2022 d'une politique visant à optimiser l'accès à des soins et à des services de santé de qualité qui sont adaptés aux besoins particuliers des patients atteints de maladies rares, et culturellement sensibles. Certains experts apprécient que le Québec soit à l'avant-garde pour la prise en charge de plusieurs maladies rares, dont le DAAT, par rapport à d'autres provinces canadiennes.

Identification and characterization of aptameric inhibitors of human neutrophil elastase.

Human neutrophil elastase (HNE) plays a pivotal role in innate immunity, inflammation, and tissue remodeling. Aberrant proteolytic activity of HNE contributes to organ destruction in various chronic inflammatory diseases including emphysema, asthma, and cystic fibrosis. Therefore, elastase inhibitors could alleviate the progression of these disorders. Here, we used the systematic evolution of ligands by exponential enrichment to develop ssDNA aptamers that specifically target HNE. We determined the specificity of the designed inhibitors and their inhibitory efficacy against HNE using biochemical and in vitro methods, including an assay of neutrophil activity. Our aptamers inhibit the elastinolytic activity of HNE with nanomolar potency and are highly specific for HNE and do not target other tested human proteases. As such, this study provides lead compounds suitable for the evaluation of their tissue-protective potential in animal models.

Regorafenib prevents the development of emphysema in a murine elastase model.

Emphysema is a chronic obstructive lung disease characterized by inflammation and enlargement of the air spaces. Regorafenib, a potential senomorphic drug, exhibited a therapeutic effect in porcine pancreatic elastase (PPE)-induced emphysema in mice. In the current study we examined the preventive role of regorafenib in development of emphysema. Lung function tests and morphometry showed that oral administration of regorafenib (5 mg/kg/day) for seven days after instillation of PPE resulted in attenuation of emphysema. Mechanistically, regorafenib reduced the recruitment of inflammatory cells, particularly macrophages and neutrophils, in bronchoalveolar lavage fluid. In agreement with these findings, measurements using a cytokine array and ELISA showed that expression of inflammatory mediators including interleukin (IL)-1ß, IL-6, and CXCL1/KC, and tissue inhibitor of matrix metalloprotease-1 (TIMP-1), was downregulated. The results of immunohistochemical analysis confirmed that expression of IL-6, CXCL1/KC, and TIMP-1 was reduced in the lung parenchyma. Collectively, the results support the preventive role of regorafenib in development of emphysema in mice and provide mechanistic insights into prevention strategies. [BMB Reports 2023; 56(8): 439-444].

Protective effect of oleo-gum resin of Commiphora wightii against elastase-induced chronic obstructive pulmonary disease-linked lung inflammation and emphysema: Isolation and identification of key bioactive phytoconstituent.

ETHNOPHARMACOLOGICAL RELEVANCE: Oleo-gum resin of Commiphora wightii (Arnott) Bhandari of family Burseraceae, commonly known as 'guggul', is a well known Ayurvedic drug used traditionally to treat various disorders including respiratory ailments. However, role of C. wightii in chronic obstructive pulmonary disease (COPD) is not known. AIM: The present work was designed to investigate the protective potential of standardized C. wightii extract/and its fractions against elastase-induced COPD-linked lung inflammation and to identify key bioactive constituent(s). MATERIAL AND METHODS: C. wightii oleo-gum resin extract was prepared using Soxhlet extraction technique and the resultant extract was standardized on basis of guggulsterone content using HPLC. The extract was partitioned by different solvents in increasing order of polarity. Standardized extract/its partitioned fractions were orally administered to male BALB/c mice 1 h prior to intra-tracheal instillation of elastase (1U/mouse). Anti-inflammatory effect was evaluated by analyzing inflammatory cells and myeloperoxidase activity in lungs. The various fraction(s) were subjected to column chromatography to isolate bioactive compound. Isolated compound was identified using 1H and 13C-NMR and analyzed for assessment of several inflammatory mediators using techniques like ELISA, PCR, and gelatin zymography. RESULTS: C. wightii extract attenuated elastase-induced lung inflammation in dose-dependent manner and Ethyl acetate fraction (EAF) provided maximum protection. EAF was subjected to column chromatography followed by assessment of bioactivity of each sub-fraction, ultimately leading towards isolation of two compounds i.e. C1 and C2. C1 seems to be the key active principle of C. wightii, as it displayed significant anti-inflammatory activity against elastase induced lung inflammation while C2 largely remains ineffective. C1 was identified as mixture of E- and Z-guggulsterone (GS). Reduction in the elastase induced lung inflammation by GS was associated with downregulation of expression of several COPD linked pro-inflammatory factors such as IL-6/TNF-α/IL-1ß/KC/MIP-2/MCP-1/G-CSF as well as normalization of redox imbalance as indicated by levels of ROS/MDA/protein carbonyl/nitrite/GSH etc. Further, 21 days prolonged administration of GS (10 mg/kg b.wt; once daily) protected against elastase-induced emphysema by mitigating expression/activity of MMP-2/-9 and increasing TIMP-1 expression. CONCLUSION: Overall, guggulsterone seems to be the key bioactive constituent responsible for exerting beneficial effects of C. wightii against COPD.

Extensive Multifocal Emphysematous Osteomyelitis of Spine: A Rare Case and a Review of Literature.

BACKGROUND: Emphysematous osteomyelitis (EO) is an extremely rare form of osteomyelitis which is complicated mainly by infection with gas-forming organisms. The common causative agents of this disease are mainly members of Enterobacteriaceae family, the most common are Escherichia coli and Klebsiella pneumoniae along with anaerobes. A total of 48 cases of EO have been reported in the literature till now globally and none have documented the isolation of Corynebacterium amycolatum. CASE PRESENTATION: We report a rare case of emphysematous osteomyelitis of the spine and pelvis due to Escherichia coli along with the isolation of Corynebacterium amycolatum from the same pus samples on two consecutive occasions in a 50-year-old female with uncontrolled diabetes mellitus, who was successively treated with antibiotics and drainage of pus. We also did a brief review of the literature of all cases reported till now. CONCLUSION: The role of Corynebacterium amycolatum in the etiology of emphysematous osteomyelitis needs to be evaluated further in future studies as we cannot completely ignore its isolation in two consecutive samples as a mere contaminant.

A Case-Control Study on Risk Factors of Pulmonary Infection in Patients with Type 2 Diabetes Mellitus and Its Implications for Clinical Intervention.

Objective: To analyze the risk factors of pulmonary infection in patients with type 2 diabetes mellitus (T2DM) and its implications for clinical intervention. Methods: One hundred and twenty-five patients with type 2 diabetes treated in our hospital from January 2019 to November 2021 were divided into simple T2DM group (n = 80) and infection group (n = 45) according to whether they were complicated with pulmonary infection or not. Sputum samples of patients with infection were collected and identified by bacterial culture. The general conditions (age, sex, body mass index, course of disease, and length of stay), pulmonary complications (chronic bronchitis, emphysema, and obstructive pulmonary disease,), blood glucose control (fasting blood glucose and glycosylated hemoglobin), and treatment (use of hormones and antibiotics and invasive operation) were compared between the two groups. Univariate and multivariate analyses were used to screen the risk factors of pulmonary infection in patients with T2DM. Results: A total of 45 patients were found to be infected in this study. 68 pathogenic bacteria were detected in the sputum samples, of which 42 were Gram-negative (61.76%), 22 were Gram-positive (35.35%), and 4 were fungi (5.88%). Gram-negative bacteria were mainly Klebsiella pneumoniae, accounting for 25.00%, followed by Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Gram-positive bacteria were mainly Staphylococcus aureus, accounting for 17.65%, followed by Streptococcus pneumoniae and Staphylococcus haemolyticus. The main fungi were Candida albicans (4.41%). The age, the course of T2DM, and the duration of hospitalization in the coinfection group were significantly higher than those in the T2DM group (P < 0.05). There was no significant difference in other indexes (P > 0.05). The number of patients with chronic bronchitis, emphysema, and obstructive pulmonary disease in the coinfection group was significantly higher than that in the T2DM group. The fasting blood glucose and glycosylated hemoglobin in the coinfection group were significantly higher than those in the T2DM group. The number of patients using hormone and antimicrobial agents and invasive operation in the coinfection group was higher than that in the simple T2DM group, and the difference was statistically significant (P < 0.05). Multivariate analysis showed that age, course of T2DM, length of hospital stay, complicated pulmonary disease, glycosylated hemoglobin, use of hormones and antibiotics, and invasive operation were all risk factors of pulmonary infection in patients with T2DM (P < 0.05). Conclusion: Gram-negative bacteria are the main pathogens of T2DM complicated with pulmonary infection. Drug sensitivity test should be combined to understand the drug resistance of pathogenic bacteria and use drugs reasonably to patients. Among them, advanced age, long course of T2DM, long hospital stay, complicated pulmonary disease, high level of glycosylated hemoglobin, use of hormones and antibiotics, and invasive operation were all risk factors of pulmonary infection in patients with T2DM. In clinical treatment, under the premise of using insulin to control blood sugar in an appropriate range, antibiotics should be used reasonably, pulmonary complications should be treated actively, pulmonary ventilation function should be improved, and invasive operation should be avoided as far as possible, which can effectively prevent the occurrence of T2DM complicated with pulmonary infection.

Post periorbital carboxytherapy orbital emphysema: a case report.

Periorbital carboxytherapy is used as one of the non-surgical facial rejuvenation methods in recent years. In this modality, the sterile carbon dioxide is injected into the subcutaneous space, assuming that to improve blood supply and repair of the injection site. Here, we report a 24- year-old woman who presented with acute bilateral orbital emphysema starting one day after cosmetic periorbital carboxytherapy. On physical examination, bilateral non-tender, non-erythematous swelling of both upper and lower lids was noted with crepitus on palpation. Uncorrected visual acuity (UCVA) of the patient in both eyes was 10/10 and RAPD was negative. The orbital computed tomography (CT) scan of the patient confirmed bilateral preseptal emphysema extending into orbital space through the orbital septum. Oral prednisolone 50 mg per day was prescribed, and the patient was observed closely. Gradually, periorbital pain and swelling subsided, and the symptoms resolved within one week.

A rare emphysematous splenic infection caused by diabetes mellitus: a case report.

Emphysematous splenic infection is a rare disease. In this case, a 33-year-old woman presented to the emergency department with a 10-day history of left-upper-quadrant abdominal pain and intermittent fever. She positively denied any previous history of illness or trauma. On admission to the hospital, her white-cell count, neutrophil percentage, C-reactive protein level, blood glucose, and urine glucose were higher than normal. Computed tomography (CT) revealed gas-fluid levels and infection in the spleen. After multidisciplinary consultation and discussions, the patient was diagnosed with emphysema spleen infection and diabetes, and the infection was most likely related to the diabetes. The patient was treated with antibiotics, hypoglycemic therapy, and transabdominal spleen infection puncture and drainage. Finally, the patient's infection and blood sugar were controlled, and the drainage fluid was unobstructed. To the best of our knowledge, emphysematous spleen infection has only been reported once previously in a super obese female patient in 2007. Interestingly, the patient in the present case was also an obese and diabetic middle-aged woman. Similar to other documented emphysematous infection cases, the disease onset of our patient was indistinct and insidious. Due to advances in imaging tools and knowledge of emphysematous nephritis, the patient was successfully diagnosed and treated in time.

[A Case of Emphysematous Pyelonephritis after Starting Treatment for Acute Pyelonephritis].

A 68-year-old man sought evaluation at our emergency department in the early morning of day X with a feverfor3 days. The physical examination revealed pain in the left back, and an abdominal computed tomography (CT) showed a high density of fatty tissue around the left kidney. With a diagnosis of left acute bacterial pyelonephritis, he was hospitalized, antibacterial drug treatment was started, and he was transferred to our department on the same day. He had uncontrolled type 2 diabetes mellitus and had been treated with multiple drugs at another hospital. A decrease in blood pressure and respiratory failure was observed at night, and when contrast CT was performed the next morning, emphysema was observed in the parenchyma of the left kidney. The patient was diagnosed with class 2 left emphysematous pyelonephritis according to the classification of Huang et al. Double J stenting in the left ureter and conservative treatment were performed. Antibiotic treatment was continued and CT-guided percutaneous catheter drainage was performed on day 11. His general condition improved and he was discharged on day 32.

Therapeutic Targeting of MMP-12 for the Treatment of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a lung disorder characterized by progressive airflow obstruction associated with inflammation and emphysema, and it is currently one of the leading causes of death worldwide. Recent studies with genetically engineered mice reported that during pulmonary inflammation, basophil-derived interleukin-4 can act on lung-infiltrating monocytes causing aberrant expression of the matrix metalloproteinase-12 (MMP-12). MMP-12 activity in turn causes the destruction of alveolar walls leading to emphysema, making it potentially a valid target for pharmacological intervention. Using nuclear magnetic resonance (NMR)- and structure-based optimizations, the current study reports on the optimized novel, potent, and selective MMP-12 inhibitors with single-digit nanomolar affinity in vitro and in vivo efficacy. Using a murine model of elastase-induced emphysema we demonstrated that the most potent agents exhibited a significant decrease in emphysema-like pathology compared to vehicle-treated mice, thus suggesting that the reported agents may potentially be translated into novel therapeutics for the treatment of COPD.

Use of Hyaluronic Acid (HA) in Chronic Airway Diseases.

Hyaluronic acid (HA) is a key component of the extracellular matrix of the lungs. A unique attribute of HA is its water-retaining properties, so HA has a major role in the regulation of fluid balance in the lung interstitium. Hyaluronic acid has been widely used in the treatment of eyes, ears, joints and skin disorders, but in the last years, it has been also proposed in the treatment of certain lung diseases, including airway diseases, due to its anti-inflammatory and water-binding capacities. Hyaluronic acid aerosol decreases the severity of elastase-induced emphysema in murine models, prevents bronchoconstriction in asthmatics and improves some functional parameters in chronic obstructive pulmonary disease (COPD) patients. Due to the protection of HA against bronchoconstriction and its hydration properties, inhaled HA would increase the volume of airway surface liquid, resulting in mucus hydration, increased mucous transport and less mucous plugging of the airways. In addition, it has been seen in human studies that the treatment with nebulised HA improves the tolerability of nebulised hypertonic saline (even at 6% or 7% of concentration), which has been demonstrated to be an effective treatment in bronchial secretion management in patients with cystic fibrosis and bronchiectasis. Our objective is to review the role of HA treatment in the management of chronic airway diseases.

NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice. NOXO1 is consistently upregulated in two models of lung emphysema, Cybb (also known as NADPH oxidase 2, Nox2)-knockout mice and wild-type mice with tobacco-smoke-induced emphysema, and in human COPD. Noxo1-knockout mice are protected against tobacco-smoke-induced pulmonary hypertension and emphysema. Quantification of superoxide, nitrotyrosine and multiple NOXO1-dependent signalling pathways confirm that peroxynitrite formation from nitric oxide and superoxide is a driver of lung emphysema. Our results suggest that NOXO1 may have potential as a therapeutic target in emphysema.