E-cigarette or vaping product use-associated lung injury.

E-cigarette or vaping product use-associated lung injury is a recently recognised, acute pulmonary syndrome which has been reported (particularly from June to October 2019) throughout the USA, but not in Europe (although one probable case, in the UK, has been reported; Medicines and Healthcare products Regulatory Agency, 2020). It presents acutely, most often in young men, as severe pulmonary consolidation, usually with respiratory failure. The mortality is around 2%. The cause(s) are unknown, but it is associated with vaping, particularly using unlicensed cannabis-containing products with tetrahydrocannabinol. Vitamin E acetate, often present in tetrahydrocannabinol-containing vape products as a solvent, has been implicated, as it has been identified in the bronchoalveolar lavage fluid of patients with e-cigarette or vaping product use-associated lung injury. This article reviews the recent literature, including clinical features, presentation and investigations, and possible mechanisms, in the context of vaping practices in the USA and the UK.

Marijuana and the lung: hysteria or cause for concern?

Increasing cannabis use and legalisation highlights the paucity of data we have on the safety of cannabis smoking for respiratory health. Unfortunately, concurrent use of tobacco among marijuana smokers makes it difficult to untangle individual effect of marijuana smoking. Chronic cannabis only smoking has been shown in large cohort studies to reduce forced expiratory volume in 1 s/forced vital capacity via increasing forced vital capacity in chronic use contrary to the picture seen in tobacco smoking. The cause of this is unclear and there are various proposed mechanisms including respiratory muscle training secondary to method of inhalation and acute anti-inflammatory effect and bronchodilation of cannabis on the airways. While cannabis smoke has been shown to increase symptoms of chronic bronchitis, it has not been definitively shown to be associated with shortness of breath or irreversible airway changes. The evidence surrounding the development of lung cancer is less clear; however, preliminary evidence does not suggest association. Bullous lung disease associated with marijuana use has long been observed in clinical practice but published evidence is limited to a total of 57 published cases and only one cross-sectional study looking at radiological changes among chronic users which did not report any increase in macroscopic emphysema. More studies are required to elucidate these missing points to further guide risk stratification, clinical diagnosis and management. KEY POINTS: Cannabis smoking has increased and is likely to increase further with relaxation of legalisation and medicinal use of cannabinoids.Chronic marijuana smoking often produces symptoms similar to those of chronic tobacco smoking such as cough, sputum production, shortness of breath and wheeze.Cessation of marijuana smoking is associated with a reduction in respiratory symptoms and no increased risk of chronic bronchitis.Spirometry changes seen in chronic marijuana smokers appear to differ from those in chronic tobacco smokers. In chronic marijuana smokers there is an increase in FVC as opposed to a definite decrease in FEV1.Multiple case series have demonstrated peripheral bullae in marijuana smokers, but no observational studies have elucidated the risk.There is currently no clear association between cannabis smoking and lung cancer, although the research is currently limited. EDUCATIONAL AIMS: To update readers on legalisation of recreational and medicinal cannabis.To summarise the evidence base surrounding the respiratory effects of inhaled marijuana use.To provide clinicians with an understanding of the main differences between cannabis and tobacco to be able to apply this to patient education.To highlight common respiratory problems among cannabis users and the need for recreational drug history taking.

Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review.

As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes.

Prolonged B cell depletion with rituximab is effective in treating refractory pulmonary granulomatous inflammation in granulomatosis with polyangiitis (GPA).

Pulmonary nodule formation is a frequent feature of granulomatosis with polyangiitis (GPA). Traditional induction therapy includes methotrexate or cyclophosphamide, however, pulmonary nodules generally respond slower than vasculitic components of disease. Efficacy of rituximab (RTX) solely for the treatment of pulmonary nodules has not been assessed. In this observational cohort study, we report patient outcomes with RTX in GPA patients with pulmonary nodules who failed to achieve remission following conventional immunosuppression. Patients (n = 5) with persistent pulmonary nodules were identified from our clinic database and retrospectively evaluated. Systemic manifestations, inflammatory markers, disease activity, concurrent immunosuppression, and absolute B cell numbers were recorded pre-RTX and at 6 monthly intervals following treatment. Chest radiographs at each time point were scored by an experienced radiologist, blinded to clinical details. Five patients with GPA and PR3-ANCA were evaluated (2 male, 3 female), mean age 34 (22-52) years. Pulmonary nodules (median 4, range 2-6), with or without cavitation were present in all patients. RTX induced initial B cell depletion (<5 cells/µL) in all patients but re-population was observed in 3 patients. Repeated RTX treatment in these 3 and persistent B cell depletion in the whole cohort was associated with further significant radiological improvement. Radiographic scoring at each time interval showed reduction in both number of nodules (P =  <0.0001) and largest nodule diameter (P =  <0.0001) in all patients for at least 18 months following B cell depletion. In summary, RTX therapy induces resolution of pulmonary granulomatous inflammation in GPA following prolonged B cell depletion.

Effect of adding postoperative noninvasive ventilation to usual care to prevent pulmonary complications in patients undergoing coronary artery bypass grafting: a randomized controlled trial.

OBJECTIVE: We compared the efficacy of noninvasive ventilation with bilevel positive airway pressure added to usual care versus usual care alone in patients undergoing coronary artery bypass grafting. METHODS: We performed a 2-group, parallel, randomized controlled trial. The primary outcome was time until fit for discharge. Secondary outcomes were partial pressure of carbon dioxide, forced expiratory volume in 1 second, atelectasis, adverse events, duration of intensive care stay, and actual postoperative stay. RESULTS: A total of 129 patients were randomly allocated to bilevel positive airway pressure (66) or usual care (63). Three patients allocated to bilevel positive airway pressure withdrew. The median duration of bilevel positive airway pressure was 16 hours (interquartile range, 11-19). The median duration of hospital stay until fit for discharge was 5 days for the bilevel positive airway pressure group (interquartile range, 4-6) and 6 days for the usual care group (interquartile range, 5-7; hazard ratio, 1.68; 95% confidence interval, 1.08-2.31; P = .019). There was no significant difference in duration of intensive care, actual postoperative stay, and mean percentage of predicted forced expiratory volume in 1 second on day 3. Mean partial pressure of carbon dioxide was significantly reduced 1 hour after bilevel positive airway pressure application, but there was no overall difference between the groups up to 24 hours. Basal atelectasis occurred in 15 patients (24%) in the usual care group and 2 patients (3%) in the bilevel positive airway pressure group. Overall, 30% of patients in the bilevel positive airway pressure group experienced an adverse event compared with 59% in the usual care group. CONCLUSIONS: Among patients undergoing elective coronary artery bypass grafting, the use of bilevel positive airway pressure at extubation reduced the recovery time. Supported by trained staff, more than 75% of all patients allocated to bilevel positive airway pressure tolerated it for more than 10 hours.

Pulmonary-renal syndrome: a life threatening but treatable condition.

Pulmonary renal syndrome (PRS) describes the occurrence of renal failure in association with respiratory failure, characterised by autoimmune-mediated rapidly progressive glomerulonephritis (RPGN) and diffuse alveolar haemorrhage (DAH), respectively. PRS is associated with significant morbidity and mortality, and prompt diagnosis and treatment significantly improve outcomes. Prompt diagnosis of PRS requires a high index of suspicion, as clinical features are non-specific, and immunological testing aids the diagnosis in many cases. The diagnostic evaluation of DAH and RPGN is outlined in the context of the important differential diagnoses. The commonest causes of PRS include antineutrophil cytoplasm antibody (ANCA)-associated vasculitis and antiglomerular basement membrane disease. As such, more emphasis has been placed on these two conditions in addition to an overview of the less common causes of PRS. We provide a practical review of the diagnostic evaluation, current treatment strategies and clinical outcomes of PRS for renal, respiratory and general physicians.

Interstitial lung disease and ANCA-associated vasculitis: a retrospective observational cohort study.

OBJECTIVES: ANCA-associated vasculitis and interstitial lung disease (ILD) are uncommon conditions. The occurrence of both diseases in the same patient is increasingly recognized. Our aim was to ascertain the characteristics and outcomes of patients with ILD and ANCA-associated vasculitis. METHODS: A retrospective observational cohort study was performed. Patients who presented to the Hammersmith Hospital, London, with ANCA-associated vasculitis [granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis (MPA) or Churg-Strauss syndrome] who also had ILD were included. Following hospital discharge, all patients were followed up in a multi-disciplinary vasculitis clinic. We recorded patient demographics, diagnostic tests, treatment, complications and mortality. RESULTS: ILD was observed in 2.7% (n = 14) of our patients with ANCA-associated vasculitis (n = 510); all had MPO-ANCA and a clinical diagnosis of MPA, giving a prevalence of 7.2% in patients with MPA (n = 194). There was no significant difference in survival between patients with MPA and ILD and those with MPA alone. CONCLUSION: It is important that physicians are aware of this clinical association and the presence of ILD should be considered in all patients with ANCA-associated vasculitis, especially those with MPO-ANCA. The possibility that patients with ILD may subsequently develop features of systemic vasculitis should also be remembered.

A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency.

Adenosine deaminase (ADA) deficiency is an inherited disorder which leads to elevated cellular levels of deoxyadenosine triphosphate (dATP) and systemic accumulation of its precursor, 2-deoxyadenosine. These metabolites impair lymphocyte function, and inactivate S-adenosylhomocysteine hydrolase (SAHH) respectively, leading to severe immunodeficiency. Enzyme replacement therapy with polyethylene glycol-conjugated ADA is available, but its efficacy is reduced by anti-ADA neutralising antibody formation. We report here carrier erythrocyte encapsulated native ADA therapy in an adult-type ADA deficient patient. Encapsulated enzyme is protected from antigenic responses and therapeutic activities are sustained. ADA-loaded autologous carrier erythrocytes were prepared using a hypo-osmotic dialysis procedure. Over a 9-yr period 225 treatment cycles were administered at 2-3 weekly intervals. Therapeutic efficacy was determined by monitoring immunological and metabolic parameters. After 9 yr of therapy, erythrocyte dATP concentration ranged between 24 and 44 micromol/L (diagnosis, 234) and SAHH activity between 1.69 and 2.29 nmol/h/mg haemoglobin (diagnosis, 0.34). Erythrocyte ADA activities were above the reference range of 40-100 nmol/h/mg haemoglobin (0 at diagnosis). Initial increases in absolute lymphocyte counts were not sustained; however, despite subnormal circulating CD20(+) cell numbers, serum immunoglobulin levels were normal. The patient tolerated the treatment well. The frequency of respiratory problems was reduced and the decline in the forced expiratory volume in 1 s and vital capacity reduced compared with the 4 yr preceding carrier erythrocyte therapy. Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective.

Inhaled therapy in elderly COPD patients; time for re-evaluation?

OBJECTIVE: chronic obstructive pulmonary disease (COPD) prevalence steadily increases with age. However, the effectiveness of inhaled therapy in the elderly COPD population has rarely been formally evaluated. We studied a group of elderly patients with COPD with a range of severity, selected from one General Practice register to measure peak inspiratory flow (PIF) and assess patient perceived benefit. METHODS: we recruited 53 randomly selected elderly patients with COPD (36 males) with a mean age of 73.5 years (range 65-89 years). The evaluation consisted of (i) information obtained from directed questions and (ii) objective measurements of the ability to generate adequate PIF for a variety of inhalers. Patients answered questions regarding ease of use, perceived benefit from and specific problems encountered with their inhaler. Three recordings of PIF were measured at varying inhaled resistances using the 'In-Check Dial'. RESULTS: thirty-five were classified as mild, 17 moderate and 1 severe COPD. All patients used a metered dose inhaler (pMDI), and 12 of the patients also used a dry powder inhaler (DPI). Forty six per cent of patients using a pMDI and 17% of those using a DPI rated their device difficult to use. No patient used a nebuliser. Thirty-one of the 53 patients using just a pMDI felt they were able to perceive benefit in comparison to 4 of the 12 DPI users. Even though most DPI users (10/12) had rated their inhaler as easy to use, 50% were 'unsure' as to whether they received any clinical benefit. Most patients were unable to generate sufficient inspiratory flow to use the higher resistance DPI's and patients with COPD who were able to generate adequate PIF were invariably mild. A significant negative correlation was found between age and the PIF achieved when assessed using the high resistance device setting (R = 0.84, P<0.0001). Multivariate analysis showed the effect of age on PIF was independent of the disease grade. CONCLUSIONS: elderly patients with COPD, even when in a stable clinical condition, may be unable to gain optimum benefit from their inhaler.

Peripheral pulmonary artery pseudoaneurysms and massive hemoptysis.

OBJECTIVE: The aim of this study was to determine the incidence and etiology of pulmonary artery pseudoaneurysms in patients undergoing bronchial angiography for massive hemoptysis and to assess patient outcome after the embolization of these pseudoaneurysms. CONCLUSION: Peripheral pulmonary artery pseudoaneurysms occur in up to 11% of patients undergoing bronchial angiography for hemoptysis. These are often most easily appreciated on bronchial and/or nonbronchial systemic arterial angiograms because of complete reversal of flow in pulmonary artery branches in the diseased lung. Embolization of bronchial and nonbronchial systemic arteries alone may not be sufficient therapy to control hemoptysis, and occlusion of the pseudoaneurysm itself via a pulmonary artery approach is recommended.

The effect of the steroid-sparing response to low-dose methotrexate on bone metabolism in glucocorticoid-dependent asthmatics.

BACKGROUND: The skeletal effects of low-dose methotrexate (MTX), in glucocorticoid-dependent asthmatics (GCDA), are unknown. METHODS: We studied 9 patients from a total of 26 chronic GCDA who completed 28 weeks of MTX (15 mg weekly, intramuscularly). Prednisolone dose was not altered during the first 12 weeks, and was then reduced between 12 and 28 weeks. Mean (S.E.M.) age of the patients was 54 (4.0) years. They had normal bone mineral density (BMD), were not taking medication that affected bone metabolism (except prednisolone and inhaled corticosteroids) and all achieved at least 50% reduction in prednisolone dose at 28 weeks. Blood and urine samples were obtained at baseline, 12, 28 and 40 weeks for measurement of serum osteocalcin (OC) and bone alkaline phosphatase (Bone-ALP) as formation markers and urinary deoxypyridinoline (DPD) and N-terminal cross-linked telopeptide of type I collagen (NTX-I) as resorption markers. RESULTS: Concurrently with the changes in prednisolone dosage serum OC levels increased significantly at 28 weeks (p<0.008) (8.1+/-1.0 ng/ml) compared to baseline (4.7+/-0.6 ng/ml) and 12 weeks (5.1+/-0.6 ng/ml), but trended back by 40 weeks (6.6+/-0.6 ng/ml). No significant changes were observed for the other bone markers between baseline and the other time points. CONCLUSIONS: The beneficial effects of steroid reduction on bone metabolism do not appear to be impaired by concomitant MTX treatment at least over 12 weeks.