Investigating the association between asthma and opioid use disorder with interactions of anxiety and depression among a national sample of the US population.

INTRODUCTION: Previous studies have not examined the association between asthma and opioid use disorder (OUD) in a comprehensive national sample of the U.S. population. This study aims to investigate such an association. METHODS: This is a matched retrospective cohort study, with a follow-up period of two years, utilizing longitudinal electronic medical records of a comprehensive national healthcare database in the U.S.-Cerner-Real World DataTM. Patients selected for analysis were ≥12 years old with a hospital encounter between January 2000 and June 2020. Adjusted risk ratios (aRRs) of incident OUD for those with asthma compared to those without asthma were calculated using a modified Poisson regressions with robust standard errors via the Huber-White sandwich estimator, and results were stratified by comorbid mental illnesses. RESULTS: Individuals with asthma had a greater risk of OUD compared to those without asthma (aRR = 2.12; 95% CI 2.03-2.23). When stratified by anxiety and depression status, individuals with asthma and no anxiety or depression had a greater risk of incident OUD compared to individuals with asthma and either anxiety, depression, or both. Additionally, individuals with asthma medication had 1.29 (95% CI: 1.24, 1.35) greater overall risk for incident OUD compared to those without medication. Independent of comorbid mental illnesses, individuals with asthma medication had greater risk for incident OUD compared to those without medication among individuals without severe/obstructive asthma. CONCLUSIONS: Individuals with asthma face a higher OUD risk compared to those without asthma. Comorbid mental illnesses modulate this risk. Caution is advised in opioid prescribing for asthma patients.

Preexisting psychological illness and its association with mortality in lung cancer patients with access to support resources.

INTRODUCTION: Diagnosis of lung cancer often results in tremendous stress for most patients, especially in patients with underlying psychological illness. Psychosocial support (consultation with psychologist, psychotherapist, or social worker) referral is considered standard for quality cancer care; however, which patients utilize these resources and how these resources affect patient outcomes remain unclear. OBJECTIVES: We aimed to identify which newly diagnosed lung cancer patients accessed available psychosocial resources and assessed how utilization of these resources correlated with treatment and survival outcomes. METHODS: Data were collected from National Cancer Institute-designated cancer center at the University of New Mexico. We analyzed lung cancer registry and mortality data at the cancer center and bronchoscopy suite data to retrospectively identify patients diagnosed with lung cancer between 2012 and 2017. We used a logistic regression model to compare psychological support utilization at the cancer center between patients with and without history of psychiatric illness. We used a Cox proportional hazards model to identify individual risk factors for mortality. RESULTS: Patients with a previous psychological diagnosis were 2.4 times more likely (odds ratio = 2.443; confidence interval [CI], 1.130-5.284) to utilize psychological resources than patients without a pre-cancer psychological diagnosis. Patients who received psychosocial intervention had a 120.4% higher hazard of dying than those who did not (hazard ratio = 2.204; 95% CI, 1.240-3.917). One-year survival probability among those who did not utilize resources was 62.65% (95% CI, 55.24%-71.06%) and 43.0% (95% CI, 31.61%-58.50%) among those who did. Patients with a previous psychiatric diagnosis were more likely to utilize psychosocial resources within 1 year of lung cancer diagnosis. CONCLUSIONS: Patients with previous psychiatric illness are more likely to utilize psychosocial resources at the cancer center after a new diagnosis of lung cancer. Patients who utilize psychosocial interventions have higher 1-year mortality than those who do not.

Bronchopleural Fistula as a Complication in a COVID-19 Patient Managed With Endobronchial Valves.

Bronchopleural fistula (BPF) is associated with high morbidity if left untreated. Although rare, the frequency of BPF in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming recognized in medical literature. We present a case of a 64-year-old male with BPF with persistent air leak due to SARS-CoV-2 pneumonia treated with Spiration Valve System endobronchial valve (EBV). An EBV was placed in the right middle lobe with successful cessation of air leak. In conclusion, the use of EBVs for BPF with persistent air leaks in SARS-CoV-2 patients who are poor surgical candidates is effective and safe.

HIF-1α Plays a Critical Role in the Gestational Sidestream Smoke-Induced Bronchopulmonary Dysplasia in Mice.

RATIONALE: Smoking during pregnancy increases the risk of bronchopulmonary dysplasia (BPD) and, in mice, gestational exposure to sidestream cigarette smoke (SS) induces BPD-like condition characterized by alveolar simplification, impaired angiogenesis, and suppressed surfactant protein production. Normal fetal development occurs in a hypoxic environment and nicotinic acetylcholine receptors (nAChRs) regulate the hypoxia-inducible factor (HIF)-1α that controls apoptosis and angiogenesis. To understand SS-induced BPD, we hypothesized that gestational SS affected alveolar development through HIF-1α. METHODS: Pregnant BALB/c mice were exposed to air (control) or SS throughout the gestational period and the 7-day-old lungs of the progeny were examined. RESULTS: Gestational SS increased apoptosis of alveolar and airway epithelial cells. This response was associated with increased alveolar volumes, higher levels of proapoptotic factors (FOXO3a, HIPK2, p53, BIM, BIK, and BAX) and the antiangiogenic factor (GAX), and lower levels of antiapoptotic factors (Akt-PI3K, NF-κB, HIF-1α, and Bcl-2) in the lung. Although gestational SS increased the cells containing the proangiogenic bombesin-like-peptide, it markedly decreased the expression of its receptor GRPR in the lung. The effects of SS on apoptosis were attenuated by the nAChR antagonist mecamylamine. CONCLUSIONS: Gestational SS-induced BPD is potentially regulated by nAChRs and associated with downregulation of HIF-1α, increased apoptosis of epithelial cells, and increased alveolar volumes. Thus, in mice, exposure to sidestream tobacco smoke during pregnancy promotes BPD-like condition that is potentially mediated through the nAChR/HIF-1α pathway.

HIV gp120 induces mucus formation in human bronchial epithelial cells through CXCR4/α7-nicotinic acetylcholine receptors.

Lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and lung infections are major causes of morbidity and mortality among HIV-infected patients even in the era of antiretroviral therapy (ART). Many of these diseases are strongly associated with smoking and smoking is more common among HIV-infected than uninfected people; however, HIV is an independent risk factor for chronic bronchitis, COPD, and asthma. The mechanism by which HIV promotes these diseases is unclear. Excessive airway mucus formation is a characteristic of these diseases and contributes to airway obstruction and lung infections. HIV gp120 plays a critical role in several HIV-related pathologies and we investigated whether HIV gp120 promoted airway mucus formation in normal human bronchial epithelial (NHBE) cells. We found that NHBE cells expressed the HIV-coreceptor CXCR4 but not CCR5 and produced mucus in response to CXCR4-tropic gp120. The gp120-induced mucus formation was blocked by the inhibitors of CXCR4, α7-nicotinic acetylcholine receptor (α7-nAChR), and γ-aminobutyric acid (GABA)AR but not the antagonists of CCR5 and epithelial growth factor receptor (EGFR). These results identify two distinct pathways (α7-nAChR-GABAAR and EGFR) for airway mucus formation and demonstrate for the first time that HIV-gp120 induces and regulates mucus formation in the airway epithelial cells through the CXCR4-α7-nAChR-GABAAR pathway. Interestingly, lung sections from HIV ± ART and simian immunodeficiency virus (SIV) ± ART have significantly more mucus and gp120-immunoreactivity than control lung sections from humans and macaques, respectively. Thus, even after ART, lungs from HIV-infected patients contain significant amounts of gp120 and mucus that may contribute to the higher incidence of obstructive pulmonary diseases in this population.

Gestational exposure of mice to secondhand cigarette smoke causes bronchopulmonary dysplasia blocked by the nicotinic receptor antagonist mecamylamine.

BACKGROUND: Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)-a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease. OBJECTIVE: We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response. METHODS: We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the gestation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth. RESULTS: Gestational but not postnatal exposure to SS caused a typical BPD-like condition: suppressed angiogenesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolarization, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the development of BPD. CONCLUSIONS: Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angiogenesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS-induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD.

Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo.

BACKGROUND: Airway mucus hypersecretion is a key pathophysiologic feature in a number of lung diseases. Cigarette smoke/nicotine and allergens are strong stimulators of airway mucus; however, the mechanism of mucus modulation is unclear. OBJECTIVES: We sought to characterize the pathway by which cigarette smoke/nicotine regulates airway mucus and identify agents that decrease airway mucus. METHODS: IL-13 and γ-aminobutyric acid type A receptors (GABA(A)Rs) are implicated in airway mucus. We examined the role of IL-13 and GABA(A)Rs in nicotine-induced mucus formation in normal human bronchial epithelial (NHBE) and A549 cells and secondhand cigarette smoke-induced, ovalbumin-induced, or both mucus formation in vivo. RESULTS: Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABA(A)R antagonist picrotoxin. Airway epithelial cells express α7-, α9-, and α10-nicotinic acetylcholine receptors (nAChRs), and specific inhibition or knockdown of α7- but not α9/α10-nAChRs abrogates mucus formation in response to nicotine and IL-13. Moreover, addition of acetylcholine or inhibition of its degradation increases mucus in NHBE cells. Nicotinic but not muscarinic receptor antagonists block allergen- or nicotine/cigarette smoke-induced airway mucus formation in NHBE cells, murine airways, or both. CONCLUSIONS: Nicotine-induced airway mucus formation is independent of IL-13, and α7-nAChRs are critical in airway mucous cell metaplasia/hyperplasia and mucus production in response to various promucoid agents, including IL-13. In the absence of nicotine, acetylcholine might be the biological ligand for α7-nAChRs to trigger airway mucus formation. α7-nAChRs are downstream of IL-13 but upstream of GABA(A)Rα2 in the MUC5AC pathway. Acetylcholine and α7-nAChRs might serve as therapeutic targets to control airway mucus.

Delayed presentation: negative pressure pulmonary hemorrhage.

Negative pressure pulmonary hemorrhage (NPPH) is a rare, life-threatening complication that develops after an acute upper airway obstruction. A 26 year old, healthy African-American man with no underlying lung disease developed negative pressure pulmonary edema and subsequently NPPH during recovery from general anesthesia for elective spine surgery. Diagnostic bronchoscopy confirmed an alveolar source of the bleeding. Clinical improvement was quick with supportive care in the medical intensive care unit.

Acute lung injury induced by Staphylococcal enterotoxin B: disruption of terminal vessels as a mechanism of induction of vascular leak.

The current hypothesis of alveolar capillary membrane dysfunction fails to completely explain the severe and persistent leak of protein-rich fluid into the pulmonary interstitium, seen in the exudative phase of acute lung injury (ALI). The presence of intact red blood cells in the pulmonary interstitium may suggest mechanical failure of pulmonary arterioles and venules. These studies involved the pathological and ultrastructural evaluation of the pulmonary vasculature in Staphylococcal enterotoxin B (SEB)-induced ALI. Administration of SEB resulted in a significant increase in the protein concentration of bronchoalveolar lavage fluid and vascular leak in SEB-exposed mice compared to vehicle-treated mice. In vivo imaging of mice demonstrated the pulmonary edema and leakage in the lungs of SEB-administered mice. The histopathological studies showed intense clustering of inflammatory cells around the alveolar capillaries with subtle changes in architecture. Electron microscopy studies further confirmed the diffuse damage and disruption in the muscularis layer of the terminal vessels. Cell death in the endothelial cells of the terminal vessels was confirmed with TUNEL staining. In this study, we demonstrated that in addition to failure of the alveolar capillary membrane, disruption of the pulmonary arterioles and venules may explain the persistent and severe interstitial and alveolar edema.

Bronchoscopic view of a tuberculosis cavity with actinomyces.

Coexistence of pulmonary actinomycosis with tuberculosis has rarely been reported. The presence of Actinomyces in sputum and bronchoalveolar lavage is inadequate for diagnosis, as it may represent mere colonization. Traditionally, excisional biopsy is considered to be the gold standard for histologic diagnosis. There are multiple case reports in which the diagnosis of pulmonary actinomycosis was based on bronchial biopsy and Wang needle aspiration. We describe an incidental finding of a bronchial communication with passage of a flexible bronchoscope into the tuberculosis cavity. The images reveal a 5-cm cavity with a whitish, stone-like structure noticed to move back and forth with respiration. Colonies of Actinomyces were seen on transbronchial brushing cytology. Bronchoalveolar lavage cultures were negative. To our knowledge such a detailed pictorial description of a tuberculosis cavity with Actinomyces has not been reported in the past.

HIV-related pulmonary hypertension.

With the availability of better treatment and prophylactic regimens for the infectious complications of human immunodeficiency virus (HIV), the non-infectious complications are gaining greater attention. HIV-related pulmonary arterial hypertension (HIV-PAH) is one of these. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals. The pathogenesis remains unclear. Patients present with symptoms as diverse as progressive shortness of breath, pedal edema, dry cough, fatigue, syncope, as well as chest pain. Chest X-ray always shows cardiomegaly and prominent pulmonary artery, and evidence of right ventricular hypertrophy can be seen from the electrocardiogram. The pulmonary arterial systolic pressure, diastolic pressure and pulmonary vascular resistance from right heart catheterization are increased. There are a few small studies showing the benefit of prostacyclin analog (epoprostenol and iloprost) and bosentan. The role of antiretrovirals remains controversial, as do those of other agents such as calcium channel blockers and anticoagulants. The prognosis of HIV-PAH is grave. Two thirds of HIV-PAH related mortality is usually secondary to consequences of pulmonary hypertension, with the worst survival noted in New York Heart Association (NYHA) functional class III-IV. The probability of survival in one series was 73%, 60% and 47% at one, two and three years, respectively.

Superior vena cava syndrome (SVC syndrome): a rare cause of conjunctival suffusion.

Obstruction of blood flow in the superior vena cava results in the signs and symptoms of superior vena cava (SVC) syndrome. Venous collaterals form, to establish alternative pathways for return of venous blood to the right atrium. The rapidity of onset of symptoms and signs from SVC obstruction is directly related to the rate at which obstruction occurs and how effective the formed collaterals are. Lung cancer and lymphoma account for more than 90% of cases of SVC syndrome. Recognition of signs and symptoms allows us to make an early diagnosis. Facial swelling, distended veins over the neck, upper extremity swelling, and dyspnea are common findings. Proptosis, periorbital swelling (including eyelid), conjunctival suffusion and elevated intraocular pressure are documented ophthalmic findings in SVC syndrome. We present a rare case of conjunctival suffusion in a 72-year-old male diagnosed with superior vena cava syndrome secondary to lung cancer.