Plans-Rubió with COPD and to present effective strategies to increase vaccination levels in patients with COPD. Virology, epidemiology, and pathophysiology of inﬂuenza The inﬂuenza virus (80–120 nm) is a member of the family Orthomyxoviridae, including three serotypes: A, B, and C (Cox et al 2000). Inﬂuenza A and inﬂuenza B are the most signiﬁcant pathogens in terms of morbidity and mortality. Type A is responsible for epidemics. Inﬂuenza C rarely produces clinical disease and has not been responsible for epidemics. The influenza virus is a negative-strand RNA virus with a genome consisting on seven (inﬂuenza C) or eight (inﬂuenza A and B) segments of RNA. Each segment of RNA is encapsided by the viral nucleoprotein (NP) and is associated with a polymerase complex. The particle consist- ing of the NP and the RNA polymerase complex is called ribonucleoprotein (RNP) particle. The RNP particles are enclosed by a protein shell called capside, formed from the assembly of helical proteins called matrix protein (M1). The capside is surrounded by a lipoprotein envelope derived from the plasma membrane of infected cells, which contain two types of spikes (8–14 nm). One spike is a box-shaped protein called neuraminidase (N) and the other spike is a protein called hemagglutinin (H). The lipid envelope contains also a tetrameric ion channel protein called M2. The influenza virus cycle can be divided into eight stages (Figure 1). Infection is initiated with the attachment of virions to susceptible host cells by reactions between the hemagglutinin particle and speciﬁc receptors on the respiratory epithelium (White and Wilson 1987) (stage 1). Receptor-bound viruses are taken into the cell by endocytosis (stage 2). Subviral particles formed by viral ribonucleoprotein (RBN) and protein M are released into the cell cytoplasm and transported into the nucleus (stage 3). In the cell nucleus, new viral RNA is formed by primary transcription (stage 4), and replication and secondary transcription of the viral RNA (stage 5). Viral proteins are formed by translation of mes- senger viral RNA (mRNA) by cell’s ribosomes (stage 6) and post-translational modiﬁcation (stage 7). The same enzyme that makes mRNA is responsible for the secondary transcrip- tion, thus replicating the viral genome. In the nucleus, M1 proteins bind to newly synthesized (-) strand viral RNAs forming RNP particles. New viral particles are formed when RNP is encased by the capside and transported to the cell surface, where they are released surrounded by a cell-derived 42 lipid membrane envelope containing hemagglutinin and neuraminidase proteins (stage 8). The hemagglutinin is responsible for both virus attach- ment and RNP release into the cell cytoplasm (White and Wilson 1987). The hemagglutinin is the major glycoprotein component of the viral envelope. It is homotrimeric and is composed of two polypeptide segments, designated HA1 and HA2. The HA1 segments form sialic acid-binding sites and mediate HA attachment to the host cell surface. The HA2 seg- ment forms the membrane-spanning anchor, and its amino- terminal region, which is called fusion peptide, appears to be directly involved in the fusion reaction mechanism. Inﬂuenza A viruses are classiﬁed into different subtypes based on their surface glycoproteins hemagglutinin (H) and neuraminidase (N). Fifteen subtypes of hemagglutinine (H1–H15) and nine subtypes of neuraminidase (N1–N9) have been identiﬁed. All of these serotypes have been found in aquatic birds. Different species of wild birds form the primary natural reservoir of the inﬂuenza A virus (Webster et al 1992). In humans, however, only three hemagglutinin proteins (H1, H2, and H3) and two neuraminidase proteins (N1 and N2) have been detected in epidemics and pandemics since 1900. Since the discovery of the inﬂuenza virus, new antigenic variants of inﬂuenza A and B have continually emerged. The inﬂuenza virus changes continually by means of two mechanisms called antigenic drift and antigenic shift (Palese and Young 1982; Kilbourne 1987). The antigenic shift is responsible for the major antigenic changes registered in human inﬂuenza A virus. The antigenic shift is produced by the reassortment of genetic components from human and nonhuman inﬂuenza viruses. The antigenic shift produces new human inﬂuenza viruses with antigenic components from the nonhuman viruses. For example, the genetic reassortment of the human inﬂuenza virus H2N2 and the avian inﬂuenza virus H3N8 can produce a new human inﬂuenza virus H3N2. Inﬂuenza pandemics are produced by the lack of a speciﬁc immune response against the new human viruses in the whole population of the world. Persons infected by one inﬂuenza vi- rus develop a speciﬁc immune response against the HN strain that is not able to recognize the new viral strain. The antigenic drift is responsible for the minor antigenic changes registered in the human inﬂuenza viruses A and B. The antigenic drift is produced by point mutations in the genetic material of existing human viruses. Persons infected by one inﬂuenza virus develop a strain-speciﬁc immune response that could not be so efﬁcient against a slightly dif- ferent virus, despite belonging to the same HN strain. For this International Journal of COPD 2007:2(1)