Cannabis-Associated Asthma and Allergies.

Inhalation of cannabis smoke is its most common use and the pulmonary complications of its use may be the single most common form of drug-induced pulmonary disease worldwide. However, the role of cannabis consumption in asthma patients and allergic clinical situations still remains controversial. To review the evidence of asthma and allergic diseases associated with the use of marijuana, we conducted a search of English, Spanish, and Portuguese medical using the search terms asthma, allergy, marijuana, marihuana, and cannabis. Entries made between January 1970 and March 2017 were retrieved. Several papers have shown the relationship between marijuana use and increase in asthma and other allergic diseases symptoms, as well as the increased frequency of medical visits. This narrative review emphasizes the importance to consider cannabis as a precipitating factor for acute asthma and allergic attacks in clinical practice. Although smoking of marijuana may cause respiratory symptoms, there is a need for more studies to elucidate many aspects in allergic asthma patients, especially considering the long-term use of the drug. These patients should avoid using marijuana and be oriented about individual health risks, possible dangers of second-hand smoke exposure, underage use, safe storage, and the over smoking of marijuana.

No gender difference in effectiveness of smoking cessation treatment in a Brazilian real-life setting.

BACKGROUND: The clinical effectiveness of pharmacotherapy for smoking cessation in real-life settings has yet to be evaluated. OBJECTIVES: To assess the effectiveness of bupropion in general clinical practice for smoking cessation and to identify predictors of failure. METHODS: In an open, non-randomised study, smokers were recruited at the Smoking Cessation Clinics, Hospital Sao Lucas, Porto Alegre, Brazil. Subjects participated in a motivational group meeting, completed a standardised questionnaire and Fagerstrom test, and had their vital signs and exhaled CO registered. All participants received a prescription of bupropion and the same cognitive behaviour therapy. They attended eight weekly individual sessions, then monthly until the sixth month and a final session at month 12. The primary outcome measure was the rate of abstinence at 12 months. The predictor factors studied were sex, age, educational level, nicotine dependence, previous attempts and comorbidities. RESULTS: Among 253 smokers (62.5% females), abstinence rates at 6 months were 20.8% for males and 22.7% for females. The success rates dropped to 13.9% and 14.3% for males and females, respectively. CONCLUSIONS: Cognitive therapy plus bupropion for smoking cessation in real-life clinics in Brazil were similar to the efficacy found in clinical trials. No significant gender differences in success rates were found.

The outcome of asthma related to workplace irritant exposures: a comparison of irritant-induced asthma and irritant aggravation of asthma.

STUDY OBJECTIVES: (1) To characterize workers' compensation claims accepted on the basis of new-onset asthma associated with accidental high respiratory irritant exposure at work; (2) to compare the frequency, characteristics, and outcomes in this group of workers to workers who were compensated for an exacerbation of preexisting asthma associated with accidental high respiratory irritant exposure at work. DESIGN: A retrospective review was performed of 469 asthma claims accepted by the Ontario Workers' Compensation Board (WCB) between 1984 and 1988. Among these, claims attributed to an accidental high respiratory irritant exposure at work were classified into two groups: one group with reported preexisting asthma prior to the exposure (accidental aggravation of asthma [AAA]) and another group with no previous history of asthma (irritant-induced asthma [IIA]). RESULTS: Of the 469 claims, 89 subjects (19%) had symptoms related to accidental high respiratory irritant exposure in the workplace; of these, 68 subjects (76%) had AAA, 12 subjects (13%) had IIA, and 9 subjects (10%) had possible IIA but were excluded from the analysis because of insufficient data. Those with IIA had a longer duration of work-attributed symptoms (mean, 219 +/- 208 days) than the subjects with AAA (mean, 32 +/- 38 days; p < 0.001). Nine subjects (75%) with IIA were no longer in the same work environment, while 47 subjects in the AAA group (71%) were still in the same work environment (p < 0.001). The most common triggering agent for subjects with IIA was an isocyanate spill; for those with AAA, the most common triggering agent was paint. CONCLUSIONS: The WCB-accepted claims related to accidental, high respiratory irritant exposure at work are more commonly assigned to the category of AAA than to IIA. IIA patients in this claimant group had a longer mean duration of work-attributed respiratory symptoms, perhaps due to a need for a larger (and thus less common) irritant exposure to induce asthma in previously normal subjects.

Nitric oxide accumulation in the nonventilated nasal cavity.

BACKGROUND: Nasal nitric oxide is present in high concentrations in the upper airway relative to the lower respiratory tract. OBJECTIVE: To explore the rate of nitric oxide accumulation in the nonventilated nasal cavity. METHODS: In 9 healthy subjects previously trained to close the soft palate, steady-state plateau nitric oxide levels were recorded while air was aspirated through the nasal airway in series at a constant flow rate. Nitric oxide was then allowed to accumulate in the nasal cavity by occluding both nares and keeping the velum closed. After varying occlusion times, peak nitric oxide levels and a second plateau were ascertained. RESULTS: While the subjects aspirated air at a constant flow, there was a slow rise to a first nitric oxide plateau. On opening to the analyzer after the accumulation period, the peak nitric oxide level was several times higher than the initial plateau (range, 2810-19008 ppb) and then slowly returned to previous plateau levels. There was no significant difference between initial and second plateau nitric oxide levels for any period. The accumulated nitric oxide peak increased in direct proportion to the accumulation time (P<.001). CONCLUSIONS: Nitric oxide concentrations accumulate in the nonventilated nasal cavity in proportion to the time of nonventilation. Peak nasal nitric oxide values after accumulation are similar to published sinus nitric oxide measurements obtained by direct puncture. These results suggest an important alternative source of nitric oxide in humans.

Unilateral nasal nitric oxide measurement after nasal surgery.

This study was designed to validate and standardize a method for unilateral nasal nitric oxide (NO) measurement. Fourteen healthy volunteers and 11 patients who had undergone unilateral medial maxillectomy were enrolled. Nasal NO was measured unilaterally by means of a dual pump system, and bilateral nasal NO was measured by aspirating air through the nasal airway in series. The median unilateral NO output was 195 nL/min on the surgical side and 291 nL/min on the contralateral, surgically untreated side (p = .006). The NO output was not significantly different between nostrils in the control group (p = .82). With the bilateral technique, there was no significant difference between the surgery group and the healthy-subjects group (p = .72). The unilateral nasal NO technique is sensitive in determining unilateral differences in nasal NO production. The NO outputs from the nostrils were similar in normal subjects regardless of the nasal cycle, but were significantly lower on the operated side in the unilateral nasal surgery group.

Aerodynamic influences on nasal nitric oxide output measurements.

Nitric oxide (NO) concentration in aspirated nasal air is flow-dependent. Nasal NO outputs calculated from steady-state plateaux at flows < 1 l/min are substantially smaller than those at flows > 2 l/min. This study aimed to determine the differences in NO output as calculated from the NO concentration plateaux in aspirated nasal air, resulting from different aspiration flows. Nasal NO was determined by chemiluminescent analysis of air obtained from the nasal passages in series during velopharyngeal closure in 8 healthy adults (flows: 0.2-3.7 l/min) and 5 with symptomatic allergic rhinitis (flows: 0.2-3.7 l/min). Mean NO output in the healthy subjects was stable at approximately 315 nl/l/min at flows of 0.2-0.7 l/min, and increased to a second steady output level of approximately 400 nl/l/min (+28%, p < 0.0001) at more physiological flow rates of 2.7 l/min and higher. The symptomatic subjects had substantially higher NO output at all flows (p < 0.001) (709.3 nl/min at 3.7 l/min) than the non-allergic subjects. The flow dependency of the nasal NO output may be explained by failure at low flows for the air stream to penetrate the peripheral parts of the complex nasal passages, and by the presence of a laminar flow regime in which a marginal lamina would tend to insulate the main stream from the mucosa. Thus, previously reported NO outputs obtained at low flows may underestimate nasal NO output compared to output at higher and more physiological transnasal airflow rates, thus affecting interpretation of results.

Aspiration flow optimized for nasal nitric oxide measurement.

The aim of the present study was to evaluate some of the factors which may influence the reliability of nasal NO measurements, and to optimize methods suitable for children and adults. Nasal nitric oxide (NO) output was determined by chemiluminescent analysis of aspirated samples in 16 adults and 6 children. With the velopharyngeal aperture closed, stable NO levels were obtained at flows ranging form 0.9 to 6.2 L/min. NO output averaged 401.0 +/- 145.4 nL/min./M2 in 6 children, 338.2 +/- 92.3 in 7 adult females and 268.6 +/- 70.2 in 9 adult males. Nasal NO output was independent of flow provided a stable plateau of NO value was reached. In this study, the optimal range of flows was 3.2-5.2 L/min. in adults and 2.2-3.2 L/min. in children. This enables selection of the most favorable flow to be chosen for individual subjects and situations.

Smoking cessation in older adults.

BACKGROUND: Older smokers are often not encouraged to quit smoking due to the erroneous idea that it is too late for such interventions. OBJECTIVE: To compare smoking cessation rates among older and younger treatment seekers, and to evaluate whether age is an obstacle to smoking cessation. DESIGN AND METHODS: Smokers (n = 987) were submitted to the same behavioural programme plus pharmacotherapy at the Smoking Cessation Clinic of Hospital Sao Lucas, in Porto Alegre, Brazil, from July 2004 to June 2009. Quit rates were evaluated at 2, 6 and 12 months. Abstinence was confirmed by exhaled carbon monoxide < 10 ppm. Volunteers were grouped by age <60 and ≥ 60 years. RESULTS: Abstinence rates (± SD) in the younger group were respectively 57.1% (± 1.9), 46.8% (± 2.1) and 43.5% (± 2.7) at 2, 6 and 12 months of follow-up. Rates for the ≥ 60 year group were respectively 67.4% (± 4.3), 52.3% (± 5.4) and 53.3% (± 5.4; log rank test, P = 0.073). The difference was also not statistically significant using Cox regression (adjusted HR 0.90, 95%CI 0.66-1.22, P = 0.48). CONCLUSIONS: In this real-world setting, treatment for smoking cessation led to similar abstinence rates in older and younger smokers. These results may have implications for clinical practice and smoking cessation policies for low- and middle-income countries such as Brazil.

Impact of a low-cost and simple intervention in enhancing treatment adherence in a Brazilian asthma sample.

The aim of this study was to evaluate adherence to treatment in persistent asthma in Brazil to determine the factors associated with non-adherence and to measure the efficacy of telephone calls in enhancing adherence. In a prospective, multicenter, interventional clinical trial with parallel groups, asthmatics were randomized into an intervention group or a control group. Asthmatics included in the intervention group received an initial telephone call to record demographic information and asthma characterization. After that, biweekly telephone calls were made to promote treatment adherence. Asthmatics included in the control group received only the initial and final telephone calls. Both groups received three packages of salmeterol/fluticasone for 3 months. The main outcome measure was the percentage of participants who took the prescribed doses of the drug. A total of 271 patients were included. The overall adherence rate was 51.9% for the control group and 74.3% for the intervention group. This meant a reduction of relative risk (RRR) of 47% (p < 0.001). The number needed to treat (NNT) was 4.5. The only variable associated with better adherence was severe persistent asthma. A low-cost easily implemented intervention, tailored to each individual, enhanced the adherence rate among Brazilian asthmatic patients.

[Nitric oxide in the nose and paranasal sinuses--respiratory tract physiology in a new perspective]. / Nitrogenmonoksid i nese og bihuler--luftveienes fysiologi i et nytt perspektiv.

Nitric oxide (NO) has important functions in a variety of physiological and pathophysiological processes in the body, including vasoregulation, haemostasis, neurotransmission, immunity and respiration. The discovery of surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the understanding of airway physiology. The high NO levels in the nasal and paranasal airways contribute to the first line defence against microorganisms. Furthermore, autoinhalation of nasal NO may improve pulmonary function and other remote physiological processes. This airborne messenger system represents a new physiological concept of potential clinical importance. However, NO, like several other mediators, has a dualistic function. Airway NO levels are increased in airway inflammations, such as asthma and allergic rhinitis, but is reduced in cystic fibrosis and other conditions with ciliary dysfunction, sinusitis and after exposure to tobacco and alcohol. Consequently, NO may prove valuable as a non-invasive marker in the diagnosis and monitoring of airway pathologies.

Nitric oxide in the nasal airway: a new dimension in otorhinolaryngology.

The discovery that the gas nitric oxide (NO) is an important signaling molecule in the cardiovascular system earned its Nobel prize in 1998. NO has since been found to play important roles in a variety of physiologic and pathophysiologic processes in the body including vasoregulation, hemostasis, neurotransmission, immune defense, and respiration. The surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the field of otorhinolaryngology. NO provides a first-line defense against micro-organisms through its antiviral and antimicrobial activity and by its upregulation of ciliary motility. Nasal treatments such as polypectomy, sinus surgery, removal of hypertrophic adenoids and tonsils, and treatment of allergic rhinitis may alter NO output and, therefore, the microbial colonization of the upper airways. Nasal surgery aimed at relieving nasal obstruction may do the same but would also be expected to improve pulmonary function in patients with asthma and upper airway obstruction. NO output rises in a number of conditions associated with chronic airway inflammation, but not all of them. Concentrations are increased in asthma, allergic rhinitis, and viral respiratory infections, but reduced in sinusitis, cystic fibrosis, primary ciliary dysfunction, chronic cough, and after exposure to tobacco and alcohol. Therefore, NO, similar to several other inflammatory mediators, probably subserves different functions as local conditions dictate. At present, it seems that the measurement of NO in the upper airway may prove valuable as a simple, noninvasive diagnostic marker of airway pathologies. The objective of this review is to highlight some aspects of the origin, physiology, and functions of upper airway NO, and to discuss the particular methodological problems that result from the complex anatomy.

Sole pulmonary involvement by Langerhans' cell histiocytosis in a child.

The case of a boy aged 4 yrs and 7 months, with isolated pulmonary involvement by Langerhans' cell histiocytosis is reported. The presentation of the disease was a sudden pneumothorax, with no previous signs of respiratory disease. The case was confirmed by S-100 and MT1 antibody staining, and was treated with pulse steroids and several pleural drainages, until the boy died after a large bilateral pneumothorax.

Exhaled nitric oxide as a noninvasive assessment of chronic cough.

Exhaled nitric oxide (ENO) has been suggested as a marker of airway inflammation. This study aimed to evaluate the role of ENO in the investigation of chronic cough. We measured ENO in 38 adult patients reporting chronic cough, in 23 healthy control subjects, and in 44 asthmatics. In addition to the regular investigation, ENO was measured by a chemiluminescent analyzer using the restricted breath technique. In the chronic cough group, 30 were considered as nonasthmatic, whereas asthma was diagnosed in eight by a positive methacholine challenge. ENO values were significantly higher in patients with chronic cough attributable to asthma as compared with those with chronic cough not attributable to asthma and to healthy volunteers (75.0 ppb; 16.7 ppb; and 28.3 ppb, respectively). The sensitivity and specificity of ENO for detecting asthma, using 30 ppb as the ENO cutoff point, were 75 and 87%, respectively. The positive and negative predictive values were 60 and 93%, and the positive and negative likelihood ratios were 5.8 and 0.3, respectively. We conclude that ENO may have a role in the evaluation of chronic cough. In this group of patients, low ENO suggested little likelihood of asthma. The patients with chronic cough not attributable to asthma showed a low ENO value as compared with healthy volunteers and asthmatics.

Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function.

The following study was undertaken in order to determine how exhaled nitric oxide (eNO) levels in former smokers with chronic obstructive pulmonary disease (COPD) compared to eNO levels in patients with asthma and in healthy nonsmoking volunteers. The study also aimed to determine any relationship between eNO levels in COPD and: 1) conventional measures of lung function; and 2) inhaled corticosteroid (ICS) use. In former smokers with COPD, nonsmokers with asthma and volunteers, eNO levels, spirometry, lung volumes, carbon monoxide diffusion capacity of the lung (DL,CO) and resting oxygen saturation (Sa,O2) were measured. Median eNO was significantly higher among patients with COPD than among healthy volunteers (p = 0.003) but lower than among patients with asthma (p < 0.01). There was no significant difference in eNO levels between COPD patients using ICS and those not using ICS. By contrast, eNO was lower among asthma patients who used ICS (median 32 parts per billion (ppb); 25-75% range 16-54) than among asthma patients who did not (51 ppb; 32-87) (p = 0.034). Among patients with COPD, eNO was inversely correlated with forced expiratory volume in one second, DL,CO and Sa,O2, and was positively correlated with the residual lung volume/total lung capacity ratio. Among patients with asthma, no significant correlations were found. Exhaled nitric oxide is increased in patients with chronic obstructive pulmonary disease, an increase that is influenced by structural abnormalities of tobacco-induced lung damage.

Trends in asthma mortality in young people in southern Brazil.

BACKGROUND: Mortality from asthma increased and is now declining in some countries, but little is known about these trends in South America. OBJECTIVE: We aimed to assess trends in mortality from asthma in southern Brazil in children and young adults. METHODS: Death certificates of 425 people in the state of Rio Grande do Sul aged between 5 and 39 years in whom asthma was reported to be the underlying cause of death during the period 1970 to 1992 were reviewed. Population data were available in 10-year age groups. Testing for trends in mortality rates was conducted using linear and log-linear regression procedures. RESULTS: Asthma mortality rates in the age groups 5 to 19 and 20 to 39 years ranged between 0.04 and 0.39/100,000 and 0.28 to 0.75/100,000, respectively, and were nonuniformly distributed over the study period. The mean annual increase in rate in 5- to 19-year olds was +0.01 (95% CI 0.003 to 0.016), an average annual percentage increase of +6.8% (95% CI 3% to 11%), with a total increase of 352% between 1970 and 1992. This increase was not due to a shift in labeling from bronchitis to asthma. In the 20 to 39-year age group, asthma and bronchitis mortality rates showed no trend to increase or decrease. CONCLUSIONS: Asthma mortality in southern Brazil is low, but rose significantly between 1970 and 1992 in the 5 to 19-year age group. This trend differs from that found in other states of Brazil and several other Latin American countries. Reasons for this difference remain unclear.

PIP: Levels of mortality due to asthma are declining in some countries. To measure trends in mortality from asthma in southern Brazil among children and young adults, the death certificates of 425 people in the state of Rio Grande do Sul aged 5-39 years in whom asthma was reported to be the underlying cause of death during the period 1970-92 were reviewed. Asthma mortality rates among people aged 5-19 and 20-39 years were 0.04-0.39/100,000 and 0.28-0.75/100,000, respectively, and were nonuniformly distributed over the study period. The mean annual increase in mortality rate among 5-19 year olds was 0.01, an average annual percentage increase of 6.8%, with a total increase of 352% during 1970-92. This increase was not due to a shift in labeling from bronchitis to asthma. Among people aged 20-39 years, asthma and bronchitis mortality rates showed no trend of increase or decrease. Reasons for the dramatic increase in asthma-related mortality among 5-19 year olds are unclear.

Nasal nitric oxide is independent of nasal cavity volume.

This study was performed to evaluate the relationship between nasal nitric oxide (NO) and changes in nasal cavity volume resulting from the topical application of xylometazoline and saline and between upright and supine posture. Nasal NO was measured using a fixed high flow technique that avoids contamination with lower airways NO. In nine healthy subjects nasal NO concentration was measured by a rapid response chemiluminescent analyzer. A tapered tube was inserted in one nostril, into which room air was insufflated to produce a constant flow of 100 mL/second; another tube was inserted into the opposite nostril for NO sampling (air exit side). Subjects were instructed to keep the vellum closed while NO was sampled through a sideport connected to the analyzer. Nasal cavity volume was measured by acoustic rhinometry from a segment of the acoustic pathway, 2 to 5 cm from the nostril. Nasal cavity volume and NO measurements were made at baseline, 15 minutes, and 60 minutes after intervention (administration of saline 0.9%, xylometazoline or posture changes on 3 consecutive days). Xylometazoline produced a significant increase in nasal cavity volume, together with a significant reduction in NO level at 15 and 60 minutes after intervention. In addition, the change from seated to supine position decreased the total nasal volume significantly, but without changes in nasal NO. No correlation was found between the magnitudes of changes in nasal NO and the changes in nasal volume. Topical application of xylomethazoline resulted in increased nasal cavity volume and reduced NO output. In contrast to previous published reports, a technique using high flow rate insufflation demonstrated an abscence of correlation between the magnitudes of changes in nasal NO and nasal cavity volume brought about by decongestant, saline, or posture.

Polymorphism of 5HT2A serotonin receptor gene is implicated in smoking addiction.

Smoking behavior is influenced by genetic factors. Polymorphisms affecting the dopaminergic system have been linked to smoking habits. The aim of this study was to investigate if the T102C polymorphism of the 5-HT(2A) receptor gene is related to tobacco use, since this receptor modulates the mesolimbic dopamine system and the C allele is associated with reduced receptor gene expression. A sample of 625 subjects were genotyped and classified according to their smoking behavior (never, former, or current smokers). We found differences in the distribution of the genotypes when the current smokers were compared with the never + former smokers, suggesting that T102C polymorphism is associated with maintenance, but not with initiation of the smoking habit. The CC genotype was more frequent in the current smokers than in the never + former smokers (chi(2) = 6.825, P = 0.03). The odds ratio of being a current smoker with a CC genotype was 1.63, 95% CI 1.06-2.51.

Does nasal nitric oxide come from the sinuses?

OBJECTIVE: The purpose of this study was to assess nitric oxide (NO) output by the nose and sinuses. METHOD: In one volunteer, the osteomeatal complex and sphenoethmoidal recess were occluded to isolate the nose from the sinuses. The antrum and frontal sinus were each punctured by two catheters and irrigated with air at constant flow. Nitric oxide output and its rate of accumulation in the absence of air flow were measured in each sinus and in the adjacent nasal cavity. RESULTS: Prior to ostial occlusion, NO output in the nose was 96 nL/min. It decreased by 12% after blockage of all of the ostia. In the isolated sinuses, it was 190 nL/min (antrum) and 68 nL/min (frontal). After 5 minutes stagnation; NO concentration [NO] rose in the occluded sinuses to 24,700 nL/L in the antrum and 22,300 nL/L in the frontal sinus. In the nose, it increased to 29,000 nL/L. When the period of stagnation was prolonged in the frontal sinus, the [NO] reached a plateau. NO output and accumulation were not altered in the nose or either sinus by opening their ostia. In the antrum and frontal sinus, lidocaine reduced NO output and the rate of NO accumulation, but not in the nose. CONCLUSIONS: In this volunteer, 88% of nasal NO was derived from the nose itself. Nitric oxide exchange between the frontal sinus, antrum, and nose was negligible. In the absence of air flow, [NO] rose to a plateau in the nose and frontal sinus. Lidocaine inhibited NO output in the sinuses but not the nose.