Cured meat consumption increases risk of readmission in COPD patients

RESULTS

From the total PAC-COPD cohort (n=342), 274 patients had available information on diet. No differences regarding sociodemographic characteristics, comorbidities, dyspnoea or lung function parameters were found between patients with and without dietary information, as previously published [13]. Table 1 shows the main characteristics of the 274 COPD patients included in this study, according to daily cured meat intake level. 93% of participants were male with a mean age of 68 yrs. Most subjects had moderate-to-severe COPD (distribution in COPD severity stages: 5% mild, 52% moderate, 37% severe, and 6% very severe). Higher daily cured meat intake was positively related to younger age, current working, current smoking, higher levels of regular physical activity, and lower BMI. Moreover, higher cured meat intake was associated with higher total energy and vegetable intakes, but no relationship was observed with fruits or fish intakes. Median cured meat intake was similar across COPD severity stages (mild: 27 g·day⁻¹, moderate: 24 g·day⁻¹, severe: 21 g·day⁻¹, and very severe: 28 g·day⁻¹; p=0.210).

As shown in table 2, the median follow-up time was 2.6 yrs with a minimum of 250 days and a maximum of 1,337 days. 97 (35%) subjects had at least one COPD hospital readmission. Although 5% of patients died during follow-up, only two (1%) died before any COPD admission, thus contributing to the analysis until death.

Kaplan–Meier curves show that the time to the first COPD readmission was longer in the low cured meat intake group (p=0.028) (fig. 1). Table 3 shows that both in the crude and adjusted parametric regression survival–time models, higher cured meat intake was related to higher risk of COPD readmission (adjusted HR 2.02, 95% CI 1.31–3.12; p=0.001). The analysis with cured meats consumption as a continuous exposure yielded a positive increasing association between cured meat intake and risk of COPD readmission (fig. 2).

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Figure 1–

Kaplan–Meier survival curves of time to the first chronic obstructive pulmonary disease (COPD) hospitalisation according to cured meat intake. ––––: low cured meat intake; ----: high cured meat intake.

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Figure 2–

Hazard ratio (HR) and 95% confidence intervals (CI) of chronic obstructive pulmonary disease readmission according to cured meat intake. HR (––––) and 95% CI (----) were obtained from a parametric regression survival–time model with cured meat intake as a continuous variable, and adjusted for centered age, total caloric intake, and forced expiratory volume in 1 s (FEV₁). The baseline HR (risk of readmission when cured meats consumption equals 0 g·day⁻¹) corresponds to the risk of a patient with mean age, mean total caloric intake and mean FEV₁.

After stratification, the estimate of the association between high cured meat consumption and COPD readmission was lower in subjects treated with inhaled corticosteroids than in subjects not using this treatment (HR 1.88, 95% CI 1.16–3.05 versus HR 2.56, 95% CI 0.94–7.02), and lower in subjects with mild and moderate COPD than in severe and very severe COPD patients (HR 1.63, 95% CI 0.85–3.15 versus HR 2.29, 95% CI 1.26–4.16), although interaction terms were not statistically significant (p=0.875 and p=0.577, respectively). Stratification according to smoking status or CRP levels showed no differences in the estimates of the association between cured meats and COPD readmission.

DISCUSSION

We found that higher current cured meat consumption increases the risk of COPD readmission to hospital. These results are coherent with previous studies about cured meats and COPD incidence. Jiang et al. [4] reported in a cross-sectional study of 7,432 subjects that frequent consumption of cured meat was associated with low lung function (FEV₁) and with an increased risk of COPD. Later on, studies of two large US cohorts, one of 42,915 males and the other of 71,531 females, showed that cured meat consumption was associated with the risk of newly diagnosed COPD both in males and females [5, 6]. The hypothesis that cured meats consumption may modify the course of COPD had not been tested before, so our findings will benefit from replication in other COPD cohorts.

Experimental evidence about cured meat components supports the biological plausibility of our findings. There is evidence suggesting that nitrites could cause lung damage. In an experimental study, rats that drank water containing sodium nitrite over a 2-yr period developed pulmonary emphysema [18], although the nitrite concentrations in the study were very high and probably not comparable to those achieved in standard human diets. Biochemical evidence shows that nitrites are pro-oxidants and can generate strong oxidising reactive nitrogen species such as peroxynitrite (ONOO^-) and others [19, 20]. These reactive nitrogen species are capable of producing lung damage [8], and have been suggested to play a role in the pathogenesis of COPD [9]. Our finding of a weaker effect of high cured meat consumption in subjects treated with inhaled corticosteroids supports the role of nitrites as mediators of the association between cured meats and worse prognosis, since the anti-inflammatory properties of corticosteroids could attenuate the oxidising and pro-inflammatory effects of nitrites. Finally, it has been argued that the largest portion of the nitrite dietary intake could come from vegetables [21], via nitrate to nitrite conversion in the mouth and the stomach [22]. However, it has been shown that high nitrate intake does not cause the expected elevated gastric nitrite concentrations [23, 24], or appreciable changes in serum nitrite concentrations [25], thus enhancing the importance of cured meats as direct sources of nitrites. Another potential mechanism that could explain the deleterious effects of cured meats in COPD course involves salt, which is added during the curing process and could enhance the negative impact of cured meats through an increase of the total body water. It could be especially harmful in COPD patients with concomitant pulmonary hypertension or poor haemodynamic status, where a salt excess could worsen these conditions and ultimately increase the risk of exacerbation.

The median intake of cured meats in the cohort (23 g·day⁻¹) was equivalent to eating one slice of ham every day. It was very similar to the 20 g·day⁻¹ that was found in the 65–75-yr-old strata of a nutritional survey performed during 2002–2003 in the general population of the same geographic area of the PAC-COPD cohort [26], but higher than the consumption reported in the previously mentioned two large US cohorts [5, 6].

There is evidence that a healthy diet could be a beneficial factor in improving and/or preventing multiple chronic diseases, including chronic lung diseases [2, 3]. However, most influential COPD guidelines, such as those produced by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) or the consensus between the American Thoracic Society and the European Respiratory Society, do not include any specific dietary recommendation to COPD patients, beyond the increase of caloric intake for the prevention of weight loss [11, 27]. This study adds new evidence suggesting that in addition to a possible increase in risk of COPD associated with cured meats [4–6] these foods may also increase risk of exacerbations, thus supporting the need to consider giving specific dietary advice to COPD patients.

A limitation of the present study is the potential measurement error in the estimation of cured meat intake due to the use of a food frequency questionnaire. However, any such misclassification is probably nondifferential and therefore would lead to an underestimation of the effects of cured meats. Following this, the presence of subjects who died prior to any COPD readmission could have produced survival bias. However, the small number of deaths before the first hospital readmission (n=2 (1%)) suggests that this bias, if present, is negligible. Finally, information on dietary changes after baseline was unavailable, although, given the current COPD management, it is unlikely that a first COPD admission could promote a reduction in cured meats consumption.

The main strengths of this study are its longitudinal design along with a very accurate characterisation of the study subjects which allowed appropriate control for confounders. Importantly, the latter also included other potentially relevant food groups such as fruits, vegetables and fish. During the follow-up, all hospitalisations were registered thoroughly, and only those with COPD as a main diagnosis were considered in the analysis. Finally, it is noteworthy that all subjects were recruited during their first COPD hospital admission, as we aimed to identify subjects at a similar state of disease evolution, following the evidence-based medicine recommendations for studies on prognosis [28].

In conclusion, high cured meats consumption was associated with an increase in the risk of COPD readmission in COPD patients. Given the economic and health burden of COPD hospitalisations, the assessment of the effectiveness of healthy diet advice should be considered in the future.