Table 2.
Studies that have analyzed the various consequences of infection by Pseudomonas aeruginosa in people with cystic fibrosis.
| Author/Year | Analysis | No. | Type of Study | Main Finding |
|---|---|---|---|---|
| Cuthbertson [45] 2020 | Diversity of microbiome and lung function | Sputum samples from 299 people with CF in the USA and Europe | Transversal | The less the diversity in the microbiota, the worse the lung function. As lung function declines, recognized pathogens, particularly PA, predominate in CF. PA is associated with poorer lung function. |
| Avendaño-Ortiz [51] 2019 | Immune response | 32 people with CF, 19 with PA, 15 healthy | Case/control | Infection by PA gives rise to a reduced monocyte response to various stimuli. |
| Styleman [52] 2019 | Lung function patterns | 60 CF >16 years | Transversal | Infection by PA is associated with greater obstruction. |
| Acosta [44] 2018 | Microbiota, factors associated with progression | Sputum sample from 104 people with CF aged from 18 to 22 years | Longitudinal | Reduced diversity and a greater presence of PA give rise to a more rapid decline in lung function and greater progression to severe forms leading to a transplant or death. No other microorganism increased the risk of progression. |
| Somayaji [53] 2017 | Impact of PA Prairie Epidemic Strain (PES) on morbidity-mortality | 274 adults with CF | Longitudinal 1980–2014 |
Infection by PES was associated with increased patient morbidity over three decades, manifested by a greater risk of respiratory death and/or lung transplant. |
| López-Causapé [48] 2017 | Characterization of isolations of PA in Spain | 24 CF units in Spain Sputum samples from 341 people with CF |
Transversal | The PA isolations are very diverse and genetically unrelated in Spain, with multiple combinations of virulence factors and high levels of resistance to antimicrobial drugs (apart from colistin). |
| Zemanick [54] 2013 | Consequences of primary infection by PA | 838 people with CF <12 years, with no isolations of PA prior to inclusion | Longitudinal: EPIC, followed up from 2004 to 2006 | The acquisition of PA was associated with a significant increase in the rates of exacerbations and crackles and wheezing. |
| De Dios-Caballero [47] 2016 | Patterns of infection-colonization in people with CF in Spain | 24 CF units in Spain Sputum samples from 341 people with CF |
Transversal | Chronic bronchial infection by PA in 46% of people (29% in children and 63% in adults). Chronic bronchial infection by PA and methicillin-resistant S. aureus is associated with poorer lung function. |
| Mayer-Hamblett [55] 2014 | Influence of PA phenotypes on severe exacerbations | 649 children with CF primary PA infection 2594 isolations |
Longitudinal: EPIC, 5.4 years of follow-up | Mucoid and altered motility phenotypes predicted the appearance of severe exacerbation. |
| Ramsey [56] 2014 | Lung function, CT, inflammation by BAL | 68 people with CF 48 healthy controls |
Longitudinal 3 to 7 years Case/control |
People with CF had poorer lung function. Bronchial infection by various microorganisms like PA was associated with poorer lung function. |
| Zemanick 2015 [57] | Relationship of microbiota, inflammation and lung function in exacerbations | 21 people with CF. Sputum, FRT, and blood pre- and post- exacerbation | Transversal | Anaerobes identified in sputum via sequencing were associated with less inflammation and better lung function compared to PA in an early exacerbation. |
| Dill 2013 [58] | Quality of life and PA | 333 adults with CF | Longitudinal | In the presence of S. Aureus, Burkholderia and PA were not predictors of any of the physical domains of quality of life. |
| Folescu [59] 2012 | CT in people with PA | 41 people with CF, 26 with chronic PA infection | Transversal, retrospective | The higher radiological scores in the PA group showed evidence of greater deterioration in lung function. |
| Mott [60] 2012 | Progression in CT | 143 people with CF from a screening program | Longitudinal 1 year |
The radiological progression of bronchiectasis and air entrapment were associated with the severe CFTR genotype, worse neutrophilic inflammation and lung infection. |
| Ren [61] 2012 | Lung function | 93 pre-school children with CF | Longitudinal 2 years |
Previous PA infection was associated with a higher rate of reduction in the FEF 25–75 z-score and mild thoracic-abdominal asynchrony in pre-school children with CF. |
| Taylor-Robinson [62] 2012 | Decline in lung function | 479 people with CF | Longitudinal 1969–2010 |
Infection by PA was associated with a significant increase in the rate of lung function decline (around 0.5%/year). |
| Sawicki [63] 2012 | Treatment of chronic PA infection with inhaled tobramycin | 12,740 people with CF | Longitudinal 6 years |
Positive cultures for PA and Burkholderia were associated with increased mortality. The use of inhaled tobramycin reduced mortality. |
| Ashish [64] 2012 | Impact of chronic infection by PA and LES-PA on quality of life (CFQ) | 157 people with CF 43 with chronic PA, 93 with chronic LES-PA, and 20 with no PA |
Transversal | People with LES-PA presented a poorer quality of life in most domains of the CFQ. People infected by PA only presented poorer scores than those not infected in the domain of bodily perception. |
| Konstan [65] 2012 | Decline in lung function | 4161 adults with CF | Longitudinal Follow-up of 3 to 25 years |
The mean rates of reductions in the FEV1 were −1.92 from 18 to 24 years of age and −145 ≥ 25 years. In the 18–24-year-old group, B. cepacia, the use of pancreatic enzymes, multi-resistant PA, mucoid PA, and female gender predicted a greater decline in lung function. |
| Pillarisetti [66] 2011 | Decline in lung function associated with inflammation and infection | 37 lactating people with CF in screening program FRT/BAL |
Longitudinal | The more neutrophil elastase in BAL, the poorer the lung function. Greater decline in lung function in people infected by S. aureus and PA. |
| Gangell [67] 2011 | PA and inflammation | 653 samples 215 people with CF aged up to 7 years |
Prospective BAL |
PA and Aspergillus were associated with higher levels of inflammation, particularly PA. |
| Rosenfeld [50] 2010 | Factors associated with the early acquisition of PA in young children with CF | 1117 children with CF but no PA (PA-Never) 583 children with CF and eradicated PA (PA-Past) |
Longitudinal: EPIC, follow-up from 2004 to 2006 | The PA-Never people had better lung function and fewer respiratory symptoms than those with a remote history of infection by PA. |
| Robinson [68] 2009 | PA and CT | 25 children with mild–moderate CF CT, FRT, cultures |
Transversal | The CT scores had a high correlation with the acquisition of PA, which is a clinically significant measure of the progression of lung disease. |
| Konstan [69] 2007 | Decline in lung function | 4866 children and adolescents with CF | Longitudinal Follow-up of 3 to 6 years |
Colonization by PA was associated with an increase in the rate of FEV1 loss (0.31% per year in the group aged 6–8 years and 0.22% in the 9–12 group). |
| Courtney [70] 2007 | Microbiology, genetics, and lung function | 183 adults with CF | Longitudinal 1995–2005 |
People infected with PA and Burkholderia presented higher mortality, and these pathogens were the main predictors of mortality. |
| Taccetti [71] 2005 | Early eradication of PA | Ciprofloxacin plus colistin to eradicate PA in 47 adults with CF | Case/control | After early antibiotic therapy: Period free of PA of 18 (4–80) months. Delayed deterioration of lung function in comparison with people with chronic infection. Prevention of appearance of strains of PA resistant to antibiotics. New acquisition with different genotypes of PA in 73%. |
| Li [72] 2005 | Relationship of mucous PA with morbidity, symptoms, antibodies, X-R and FRT | 56 adults with CF | Longitudinal from birth to 16 years (1985 to 2004) | The transition time of non-mucoid PA was relatively long (mean, 10.9 years). The deterioration in cough scores and X-R and the decline in lung function correlated with the transition from non-mucoid to mucoid PA. |
| Coburn [43] 2015 | Microbiome: Sequencing of ribosomal RNA | Sputum samples from 269 people with CF | Transversal | Greater diversity in the microbiome at a lower age. Less diversity correlated with poorer lung function. Greater prevalence and relative abundance of PA and Burkholderia in older people. PA was associated with poorer lung function. |
| West [27] 2002 | Cultures and antibodies against PA | 68 children screened for CF | Longitudinal 1985–2000 | In CF screening, the antibodies against PA were present 6 to 12 months before any isolation in respiratory secretions. |
| Nixon [33] 2001 | Relationship between inflammation and infection with symptoms and lung function | CF children aged under 3 years BAL Lung function |
Neonatal screening | Infection of the lower airways by various microorganisms as demonstrated by BAL was associated with a 10% reduction in the FEV (0.5) compared to subjects with no infection. |
| Emerson [49] 2002 | PA as a prognostic factor for morbidity and mortality | 3323 people with CF from the CFF-PR | Longitudinal 1990–1998 |
People with positive cultures for PA had a 2.6 times higher risk of death at 8 years and they presented a lower percentage of FEV1 and weight percentile, as well as a greater risk of hospitalization and respiratory exacerbation in the follow-up. |
| Nixon [33] 2001 | Impact of early primary infection by PA. BAL | 56 people with CF screened from 1990 to 1992 | Longitudinal Follow-up of up to 7 years |
Four children infected with mucoid, multi-resistant PA died under the age of 7. Infection by PA was associated with more morbidity, greater lung function decline, longer hospitalizations, and higher mortality. |
| Navarro [73] 2001 | Lung function | European CF Registry. 7010 people with CF |
Follow-up of 6 years | PA was associated with lower FEV1. |
| Kosorok [34] 2001 | Impact of PA Radiological score FEV1 |
56 children from CF screening program | Longitudinal | The rate of lowering of the radiological score increased after the acquisition of PA (from 0.45 to 1.40 points/year; p < 0.001). Lung function decline speeded up after the acquisition of PA, (previous FEV1/FVC decline of 1.29%/year; subsequently it was 1.81%; p = 0.001). |
| Hudson [74] 1993 | Early infection by PA and prognosis | 81 children with CF aged under 2 years at the start | Longitudinal Follow-up of 5.4 to 13 years |
Initial PA at 2 years or under was associated with increased morbidity (lower radiological score and poorer lung function). Detection of PA and S. aureus in cultures was associated with a higher mortality rate in the first 10 years after the diagnosis. |
| Henry [75] 1992 | Impact on survival of mucoid isolates of PA | 81 children with CF Sputum samples Lung function |
Longitudinal 8 years or mortality |
FEV1 was the main prognostic factor for mortality. The identification of mucoid forms of PA was an unfavorable prognostic factor. |
| Pamucku [76] 1995 | Infection by PA and lung function | 192 children with CF | Longitudinal 1982–1992 | FEV1 loss was more significant in people colonized by PA than those who were not. |
| Kerem [77] 1990 | Infection by PA and evolution of la lung function | 895 children with CF | Longitudinal from 1975 to 1998 | Prevalence of PA of 82%. At the age of 7 years, the mean percentage of predicted FEV1 was 10% lower in those children already colonized by PA, compared to those who were not (p < 0.01). |
PA: Pseudomonas aeruginosa; LES: Liverpool Epidemic Strain; CT: computerized tomography; X-R: chest X-ray; CFTR: cystic fibrosis transmembrane conductance regulator of cystic fibrosis; CFQ: quality of life questionnaire for cystic fibrosis; BAL: bronchoalveolar lavage; FRT: functional respiratory tests; FEV1: forced expiratory volume in 1 s; FEF: forced expiratory flow; EPIC: Early Pseudomonas Infection Control Observational Study. Prospective cohort study analyzing risk factors and clinical results associated with the early acquisition of PA in children with cystic fibrosis; CFF-PR: Cystic Fibrosis Foundation Patient Registry.