Future work must also continue focusing on improving functioning and symptom reduction via more comprehensive and multi-modal wrap-around services, and including empirically supported treatments for schizophrenia such as psychosocial therapy and mindfulness interventions. Given observed progressive declines in global cognitive function in patient with schizophrenia over time, increased participation in cognitive remediation training programs and/or cognitive control programs may be additionally useful. Lastly, researchers and clinicians alike should aim to reduce the gap between their respective fields in order to facilitate widespread utility of CHR classification and intervention. This likely begins with addressing classification discrepancies and refining clinical/research tools as needed; specifically, whether it is more efficacious to define psychosis from a dichotomous or continuous perspective. The adoption of low-cost screening methods may also prove fruitful here. In conclusion, many important findings in CHR research have emerged over the past year, particularly in the domain of clinical functioning. This field continues to progress in its attempts to clarify both clinical and biological markers of psychosis risk, and has begun to offer important insight into interventions for reducing the likelihood of psychosis emergence. Although more work is necessary to elucidate and expand the current literature, we have started gaining traction on utilizing research findings to reach a point of meaningful intervention and prevention of psychosis. Cigarette smoking causes and exacerbates chronic obstructive pulmonary disease and asthma,and is associated with wheezing and cough in populations without a respiratory diagnosis.Quitting cigarettes improves respiratory symptoms and limits lung function deterioration.While the relationship between cigarette smoking and respiratory symptoms is well-established, the relationship between use of other tobacco products besides cigarettes and respiratory symptoms in adults is less clear. Changes in the tobacco market, in part,mobile vertical growing racks reflect efforts to market products that may cause less harm than cigarettes. Electronic nicotine delivery devices may represent such a product. With respect to respiratory symptoms, findings have been mixed, however.

Numerous animal and in vitro studies raise theoretical concerns about e-cigarette use and lung disease.Short term human experimental studies have linked adult e-cigarette use with wheezing and acute alterations in lung function,and lower forced expiratory flow.One longer term 12-week prospective study of cigarette smokers switching to e-cigarettes found no effects on lung function,and two 1-year randomized controlled clinical trials found reduced cough and improved lung function in persons who used e-cigarettes to reduce or quit cigarettes.Cross-sectional observational studies using Waves 2 and 3 data from the Population Assessment of Tobacco and Health Study have found an association between e-cigarette use and respiratory symptoms. One longitudinal W3-W4 PATH Study analysis found no relation between exclusive e-cigarette use and incident respiratory symptoms but suggested that dual users of cigarettes and e-cigarettes had significantly higher risk for symptom onset compared to exclusive cigarette users.Finally, one prospective study of young adults found an association between cannabis vaping and respiratory symptoms.There are many design issues that make these studies hard to compare. The clinical importance of the respiratory outcome is not clear in most cases because the multiple wheezing questions are analyzed in isolation from each other, or an endorsement of only one item is considered symptomatic. Many of the studies included adults with COPD, which is a diagnosis strongly linked to a history of cigarette smoking, and many people with COPD have chronic severe wheezing and dyspnea. Another concern is residual confounding: Most of the studies showing an association between e-cigarette use and respiratory symptoms failed to adjust for cigarette smoking history and concurrent marijuana use, both associated with respiratory problems and concurrent e-cigarette use. Finally, few studies addressed alternative tobacco product categories besides e-cigarettes. To better understand these divergent findings on how tobacco product use relates to respiratory health, we analyzed W2 and W3 data from the PATH Study.We developed a dependent variable that incorporated all available questions on wheezing and nighttime cough and determined cut-off values associated with functional outcomes. We focused on both cross sectional and longitudinal associations between functionally-important respiratory symptoms and ten mutually exclusive tobacco product use categories, adjusting for past cigarette smoking history and concurrent marijuana use. We also examined results for two different cut-off values for a respiratory symptom index to test for sensitivity to symptom severity. Covariates were derived from W1 and W2, and included variables associated with both tobacco exposure and functionally-important respiratory symptoms.

Low socioeconomic status is associated with tobacco use and poorer lung function.Sociodemographic variables included age, sex, race/ethnicity, education, income, and urbanicity. Medical conditions that could result from tobacco use and also cause respiratory symptoms included asthma, congestive heart failure, heart attack, diabetes, cancer, being overweight, and use of anti-hypertensives known to cause coughing or wheezing . Smoke-related exposures included pack-years of cigarette smoking, second-hand smoke exposure, and marijuana use. Calculating pack years of smoking We were particularly concerned with adjusting results carefully for each individual’s cigarette smoking history, an important predictor of respiratory outcomes. We derived lifetime pack years to account for cigarette smoking history in this analysis. Lifetime pack years is a clinical metric calculated by multiplying the number of packs of cigarettes per day someone smokes by the number of years they have smoked cigarettes. The following text annotates the algorithm to calculate Wave 1 lifetime pack years. Data from Wave 1 lifetime pack years was used in conjunction with variables describing subsequent cigarette use to determine lifetime pack years at W2 and beyond. Never smokers were assigned a pack years value of zero. All questions used in the algorithm and response categories are listed in Supplemental Table 3. Because of routing instructions in the PATH Study interview, only those respondents who said that they have smoked cigarettes “fairly regularly” were asked about how long they have smoked or did smoke . For any respondent at Wave 1 who currently smokes regularly or formerly smoked fairly regularly, lifetime pack years was calculated by multiplying the number of cigarette packs smoked per day by the number of years they have smoked fairly regularly. Two different formulas were used for this calculation, depending onanswers to the questions for variable R01_AC9004 and R01_AC9009 . At W2, the prevalence of functionally-important respiratory symptoms was 7.2% . Table 1 shows that respiratory symptoms were more common in the four categories of tobacco use that included cigarettes , compared to never tobacco use, and among those who used marijuana. Functionally-important respiratory symptoms were much more common among those with asthma, and also more common among those with comorbid conditions, obesity, and those using medications known to cause coughing or wheezing . Figure 1 illustrates the unadjusted linear relationship between frequency of cigarette use and proportion of persons with functionally-important respiratory symptoms for the four use categories featuring cigarettes.

The shape of the dose-response lowess lines were almost identical and the 95th percentile for cigarette use intensity was essentially the same for all four groups, regardless of what other tobacco products were added to cigarettes, emphasizing the importance of cigarettes in these four most prevalent categories of tobacco use. In the full, adjusted, multi-variable cross-sectional model , all four tobacco use categories that featured cigarette smoking were associated with a doubling of the risk of functionally-important respiratory symptoms vs. never tobacco users ,mobile vertical system grow and risk for the multiple use categories were not significantly different from exclusive cigarette use . As illustrated in Figure 2, we observed a significant positive dose-response relationship for current use of cigarettes . Compared to never users, the risk of functionally-important respiratory symptoms were not significantly different for exclusive users of e-cigarette, cigar, hookah and smokeless tobacco; moreover post hoc testing indicated that risk ratios for each of these categories were significantly lower compared to exclusive cigarette use . None of these cross-sectional results changed when the analysis was repeated at a respiratory index cut-off level of ≥2. Testing sensitivity to key confounders of the e-cigarette—respiratory symptom association Cigarette smoking pack-years, second-hand smoke exposure, and marijuana use were also associated with functionally-important respiratory symptoms . Table 2 highlights the importance of cigarette smoking pack-years and past-month marijuana use as confounders of the association between tobacco product use and respiratory symptoms. Cigarette pack-years was a particularly strong confounder; adding this variable alone to the cross-sectional multi-variable model attenuated association estimates for cigarettes and cigarettes+e-cigarettes by 30% and for exclusive e-cigarettes by 25%. That was partly because all three groups had a similarly long cigarette smoking history—weighted mean 13.4 cigarette pack-years for exclusive cigarette smokers, 12.9 for the dual users, and 10.8 for exclusive e-cigarette users. Similarly, 19.2% of exclusive e-cigarette users also currently used marijuana; adding P30D marijuana use to the multi-variable model attenuated association for e-cigarettes by 9%. Adding all three confounders together attenuated the e-cigarette-respiratory symptom association RR from 1.53 to 1.05. The categorical analysis did not address whether functionally-important respiratory symptoms increased with increasing frequency of use. Figure 2 explored this for cigarettes and e-cigarettes, adjusting for cigarette smoking history. For cigarettes, there was a significant linear increase in the percent with functionally-important respiratory symptoms with higher intensity of use; prevalence of respiratory symptoms was less than 5% for never users and over 30% for those smoking a pack a day or more. There was also an increase in respiratory symptoms with higher intensity of e-cigarette use, but the trend did not reach statistical significance .There were no statistically significant associations between exclusive use of cigars, smokeless tobacco or hookah and worsening of respiratory symptoms compared to never users.

Post hoc testing indicated that risk ratios were significantly smaller than for exclusive use of cigarettes, regardless of cutoff level for the respiratory symptom outcome . In contrast, findings for exclusive e-cigarette use were sensitive to symptom severity, showing a significant association with worsening symptoms at a threshold of ≥2 , but not at a symptom threshold of ≥3 . This study underscores the adverse consequences of continued cigarette smoking among people without COPD or other non-asthma respiratory disease on functionally-important respiratory symptoms. Consistent with other studies,a longer history of cigarette smoking predicted worsening respiratory symptoms and decreased chances of improvement, independent of P30D cigarette smoking, underlining the importance of cigarette smoke exposure in the development or worsening of respiratory symptoms. The consequences of cigarette use were the same regardless of which additional tobacco products were used. As shown previously, dual users of cigarettes and e-cigarettes smoked cigarettes as frequently as exclusive cigarette smokers,their respiratory response to cigarette smoking intensity was essentially the same as exclusive cigarette users, and they had indistinguishable risk for symptom worsening.We found no evidence to support the idea that dual use of cigarettes and e-cigarettes carries higher risk for respiratory symptom worsening compared to exclusive cigarettes for the symptom outcomes we examined. This contrasts with increased risk of dual use in the analyses of PATH Study data reported by Reddy et al,an analysis that involved a different period , and adjusted only for demographics; we doubt the finding reported by Reddy would have remained statistically significant after adjustment for the multiple confounders included in the present analysis. In contrast, respiratory symptom risk for exclusive users of other tobacco products was significantly lower than for cigarettes, and was largely not significantly different from never or former tobacco users. The finding for e-cigarettes contradicts two cross-sectional studies of tobacco use and respiratory symptoms, one using PATH Study W2 data18 and one using W3 data,both concluding that there was an association between e-cigarette use and wheezing. These studies examined the association with each item on the respiratory index and neither adjusted for cigarette smoking history or marijuana use.34 Based on the present study findings— lack of a crude dose-response for e-cigarette frequency illustrated in Figure 2 and the confounding analysis in Table 2—we conclude that the reported associations in these papers were likely spurious, primarily because of the failure to adjust for cigarette smoking history. Our supplemental materials include a method for determining cigarette pack-years from PATH Study data to support the inclusion of this important confounder by other users of these data. The longitudinal results seem contradictory if the reference of focus is never users—ecigarette users are significantly more likely to have symptoms worsen at one cut-off level and significantly more likely to have symptoms improve at another—an example of how results for ecigarette users may be sensitive to how health outcomes are determined. But another viewpoint is that potentially reduced harm tobacco products are judged also by how health risks of the product compare to the health risks for cigarette smokers.